Updated on 2024/02/05

写真a

 
YUBA Eiji
 
Organization
Graduate School of Engineering Division of Science and Engineering for Materials, Chemistry and Biology Associate Professor
School of Engineering Department of Applied Chemistry
Title
Associate Professor
Affiliation
Institute of Engineering
Contact information
メールアドレス
Affiliation campus
Nakamozu Campus

Position

  • Graduate School of Engineering Division of Science and Engineering for Materials, Chemistry and Biology 

    Associate Professor  2022.04 - Now

  • School of Engineering Department of Applied Chemistry 

    Associate Professor  2022.04 - Now

Degree

  • 博士(工学) ( Others )

Research Areas

  • Nanotechnology/Materials / Polymer chemistry  / Polymer Chemistry

  • Life Science / Biomaterials  / Medical Bioengineering, Biomaterials

  • Life Science / Biomedical engineering  / Medical Bioengineering, Biomaterials

Research Interests

  • Autoimmune Diseases

  • pH-Sensitive Polymer

  • Immunoengineering

  • Nano Vaccine

  • Lymph node

  • Liposome

  • Biomaterials

  • Drug delivery system

  • Cancer immunotherapy

  • Functional polymer

  • pH-sensitivity

  • Vaccine

Research subject summary

  • 機能性脂質を用いた薬物送達システム

  • 機能性リポソームを用いた薬物送達システム

  • pH応答性高分子修飾リポソームを用いたがん治療システムの開発

  • pH応答性高分子修飾リポソームを用いたナノワクチンシステムの開発

  • pH応答性高分子を用いた細胞内への遺伝子デリバリー

  • pH応答性高分子を用いた細胞内へのタンパク質デリバリー

Research Career

  • 免疫誘導機能の統合による高活性抗原ナノキャリアの創製と免疫治療への展開

    Joint Research in Japan

    2015.04 - 2018.03 

  • 蛋白質・遺伝子の同時送達により免疫反応を精密制御できるナノワクチンキャリアの開発

    Individual

    2011 - 2015 

  • 多分岐pH応答性ポリマー修飾リポソームによる高活性型がん免疫ワクチンの開発

    Individual

    2011 

  • 高活性な免疫誘導を実現する多機能集積型ナノワクチンシステムの構築

    Individual

    2010 

  • 新規なpH応答性ポリマー修飾リポソームを用いた高活性免疫ワクチンの開発

    Individual

    2010 

Professional Memberships

  • THE JAPANESE SOCIETY FOR IMMUNOLOGY

    2018.04 - Now   Domestic

  • THE PHARMACEUTICAL SOCIETY OF JAPAN

    2013.02 - Now   Domestic

  • JAPANESE SOCIETY FOR HISTOCOMPATIBILITY AND IMMUNOGENETICS

    2012.07 - Now   Domestic

  • American Chemical Society

    2009.03 - Now   Overseas

  • THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

    2008.03 - Now   Domestic

  • 遺伝子・デリバリー研究会

    2006.07 - Now   Domestic

  • THE JAPANESE SOCIETY FOR BIOMATERIALS

    2006.07 - Now   Domestic

  • THE SOCIETY OF POLYMER SCIENCE, JAPAN

    2006.04 - Now   Domestic

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Committee Memberships (off-campus)

  • 世話人   日本バイオマテリアル学会 関西ブロック  

    2022.04 - 2023.03 

  • 評議員   日本バイオマテリアル学会  

    2020.04 - Now 

  • 世話人   第80回高分子若手研究会[関西]  

    2013.04 - 2014.03 

Awards

  • The Award for Young Investigator of Japanese Society for Biomaterials(2022)

    Eiji Yuba

    2022.11   The Japanese Society for Biomaterials   Development of Liposome-Based Immunity-Inducing Systems Using Functional Polymers

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    Country:Japan

  • The Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology: The Young Scientists’ Award

    Eiji Yuba

    2022.04   Ministry of Education, Culture, Sports, Science and Technology   Control of immune responses by functional polymers and their application to the treatments

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    Country:Japan

  • 12th Young Scientist Award (Fundamental)

    Eiji Yuba

    2020.07   The Japan Society of Drug Delivery System   Development of pH-sensitive polymer- and liposome-based immunity-inducing systems

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    Country:Japan

  • Outstanding Reviewer for Journal of Materials Chemistry B in 2018

    Eiji Yuba

    2019.03   Royal Society of Chemistry  

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    Country:United Kingdom

  • Nanomaterials 2017 Outstanding Reviewer Awards

    Eiji Yuba

    2018.03   MDPI  

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    Country:Switzerland

  • Kao Scientific Encouragement Award

    Eiji Yuba

    2017.06   The Kao Foundation for Arts and Sciences  

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    Country:Japan

  • Best Poster Paper Award

    2016.11   Biomaterials International 2016  

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    Country:Taiwan, Province of China

  • Award for Encouragement of Research in Polymer Science

    Eiji Yuba

    2015.05   The Society of Polymer Science, Japan  

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    Country:Japan

  • Biomacromolecules Best Poster Awards

    Eiji Yuba

    2014.09   3rd Symposium on Innovative Polymers for Controlled Delivery  

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    Country:China

  • Japanese and Korean Biomaterials Societies Young Scientist Exchange Program Award

    Eiji Yuba

    2013.11   Japan society for biomaterials  

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    Country:Japan

  • The academic encouraging award

    Eiji Yuba

    2012.09   Japan society for histocompatibility and immunogengetics  

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    Country:Japan

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Job Career (off-campus)

  • Cabinet Office, Government of Japan   Secretariat of Science, Technology and Innovation Policy   Fellow for Science, Technology and Innovation Policy

    2021.04 - Now

  • Cabinet Office, Government of Japan   Bureau of Science, Technology and Innovation   Fellow for Science and Technology Policy

    2020.04 - 2021.03

  • The University of Chicago   Pritzker School of Molecular Engineering   Visiting Scientist

    2019.04 - 2019.09

  • Osaka Prefecture University   Department of Applied Chemistry, Graduate School of Engineering

    2017.10 - Now

Papers

  • Reversible Stabilization of Nanofiber-Polyplexes through Introducing Cross-Linkages.

    Aono R, Nomura K, Yuba E, Harada A

    Journal of functional biomaterials   15 ( 1 )   2023.12( ISSN:2079-4983

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  • Preparing Size-Controlled Liposomes Modified with Polysaccharide Derivatives for pH-Responsive Drug Delivery Applications Reviewed

    Shin Yanagihara, Yukiya Kitayama, Eiji Yuba, Atsushi Harada

    Life   13 ( 11 )   2158 - 2158   2023.11( ISSN:2075-1729

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)  

    The liposome particle size is an important parameter because it strongly affects content release from liposomes as a result of different bilayer curvatures and lipid packing. Earlier, we developed pH-responsive polysaccharide-derivative-modified liposomes that induced content release from the liposomes under weakly acidic conditions. However, the liposome used in previous studies size was adjusted to 100–200 nm. The liposome size effects on their pH-responsive properties were unclear. For this study, we controlled the polysaccharide-derivative-modified liposome size by extrusion through polycarbonate membranes having different pore sizes. The obtained liposomes exhibited different average diameters, in which the diameters mostly corresponded to the pore sizes of polycarbonate membranes used for extrusion. The amounts of polysaccharide derivatives per lipid were identical irrespective of the liposome size. Introduction of cholesterol within the liposomal lipid components suppressed the size increase in these liposomes for at least three weeks. These liposomes were stable at neutral pH, whereas the content release from liposomes was induced at weakly acidic pH. Smaller liposomes exhibited highly acidic pH-responsive content release compared with those from large liposomes. However, liposomes with 50 mol% cholesterol were not able to induce content release even under acidic conditions. These results suggest that control of the liposome size and cholesterol content is important for preparing stable liposomes at physiological conditions and for preparing highly pH-responsive liposomes for drug delivery applications.

    DOI: 10.3390/life13112158

    PubMed

  • In vivo transfection of cytokine genes into tumor cells using a synthetic vehicle promotes antitumor immune responses in a visceral tumor model.

    Shunichi Watanabe, Ayaka Takagi, Eiji Yuba, Chie Kojima, Nanako Dei, Akikazu Matsumoto, Jun Tanikawa, Tetsuya Kawamura, Nadeeka H De Silva, Takeshi Izawa, Takashi Akazawa, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   37 ( 11 )   e23228   2023.11( ISSN:08926638

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    The tumor microenvironment (TME) strongly affects the clinical outcomes of immunotherapy. This study aimed to activate the antitumor immune response by manipulating the TME by transfecting genes encoding relevant cytokines into tumor cells using a synthetic vehicle, which is designed to target tumor cells and promote the expression of transfected genes. Lung tumors were formed by injecting CT26.WT intravenously into BALB/c mice. Upon intravenous injection of the green fluorescent protein-coding plasmid encapsulated in the vehicle, 14.2% tumor-specific expression was observed. Transfection of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and CD40 ligand (L)-plasmid combination and interferon gamma (IFNγ) and CD40L-plasmid combination showed 45.5% and 54.5% complete remission (CR), respectively, on day 60; alternate treatments with both the plasmid combinations elicited 66.7% CR, while the control animals died within 48 days. Immune status analysis revealed that the density of dendritic cells significantly increased in tumors, particularly after GM-CSF- and CD40L-gene transfection, while that of regulatory T cells significantly decreased. The proportion of activated killer cells and antitumoral macrophages significantly increased, specifically after IFNγ and CD40L transfection. Furthermore, the level of the immune escape molecule programmed death ligand-1 decreased in tumors after transfecting these cytokine genes. As a result, tumor cell-specific transfection of these cytokine genes by the synthetic vehicle significantly promotes antitumor immune responses in the TME, a key aim for visceral tumor therapy.

    DOI: 10.1096/fj.202202036R

    PubMed

  • Canvassing Prospects of Glyco-Nanovaccines for Developing Cross-Presentation Mediated Anti-Tumor Immunotherapy Reviewed International coauthorship

    Amina I. Makandar, Mannat Jain, Eiji Yuba, Gautam Sethi, Rajesh Kumar Gupta

    Vaccines   10 ( 12 )   2049 - 2049   2022.11( ISSN:2076-393X

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    In view of the severe downsides of conventional cancer therapies, the quest of developing alternative strategies still remains of critical importance. In this regard, antigen cross-presentation, usually employed by dendritic cells (DCs), has been recognized as a potential solution to overcome the present impasse in anti-cancer therapeutic strategies. It has been established that an elevated cytotoxic T lymphocyte (CTL) response against cancer cells can be achieved by targeting receptors expressed on DCs with specific ligands. Glycans are known to serve as ligands for C-type lectin receptors (CLRs) expressed on DCs, and are also known to act as a tumor-associated antigen (TAA), and, thus, can be harnessed as a potential immunotherapeutic target. In this scenario, integrating the knowledge of cross-presentation and glycan-conjugated nanovaccines can help us to develop so called ‘glyco-nanovaccines’ (GNVs) for targeting DCs. Here, we briefly review and analyze the potential of GNVs as the next-generation anti-tumor immunotherapy. We have compared different antigen-presenting cells (APCs) for their ability to cross-present antigens and described the potential nanocarriers for tumor antigen cross-presentation. Further, we discuss the role of glycans in targeting of DCs, the immune response due to pathogens, and imitative approaches, along with parameters, strategies, and challenges involved in cross-presentation-based GNVs for cancer immunotherapy. It is known that the effectiveness of GNVs in eradicating tumors by inducing strong CTL response in the tumor microenvironment (TME) has been largely hindered by tumor glycosylation and the expression of different lectin receptors (such as galectins) by cancer cells. Tumor glycan signatures can be sensed by a variety of lectins expressed on immune cells and mediate the immune suppression which, in turn, facilitates immune evasion. Therefore, a sound understanding of the glycan language of cancer cells, and glycan–lectin interaction between the cancer cells and immune cells, would help in strategically designing the next-generation GNVs for anti-tumor immunotherapy.

    DOI: 10.3390/vaccines10122049

    PubMed

  • Cationic lipid potentiated the adjuvanticity of polysaccharide derivative-modified liposome vaccines. Invited Reviewed

    Eiji Yuba, Yuna Kado, Nozomi Kasho, Atsushi Harada

    Journal of Controlled Release   362   767 - 776   2022.10( ISSN:0168-3659

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Antigen carriers that can selectively deliver antigens to antigen presenting cells and which can simultaneously activate these cells (adjuvant property) are necessary for efficient cancer immunotherapy or vaccination. Delivery of a model antigen into dendritic cell cytosol has been achieved by pH-responsive polymer-modified liposomes via destabilization of endosomal membranes responding to acidic pH, which impelled antigen-specific cellular immunity. Furthermore, β-glucan-based pH-responsive polysaccharides have shown not only cytosolic antigen delivery performance but also adjuvant property, which further heightened cellular immune responses. Because pH-responsive polysaccharides have anionic carboxy groups, cationic lipid was introduced to liposomes in this study to improve the modification efficiency of pH-responsive polysaccharides and to improve their adjuvanticity and immunity-inducing functions. Introduction of cationic lipids increased the amounts of polysaccharide derivatives on the liposome and increased the cellular association of the liposomes to dendritic cells. Liposomes containing β-glucan-based pH-responsive polysaccharides and cationic lipids increased cytokine production from dendritic cells much more than other polysaccharide derivatives did. Furthermore, through improvement of intra-tumoral immunosuppression and induction of antigen-specific cellular immunity, administering these liposomes impelled tumor suppression even with a small antigen dose. These results suggest that introducing cationic lipids and using pH-responsive polysaccharides having intrinsically adjuvant function are effective for producing liposomal nanovaccines showing strong immunity-inducing function.

    DOI: 10.1016/j.jconrel.2022.10.016

    PubMed

    Repository URL: http://hdl.handle.net/10466/0002000048

  • Programed Thermoresponsive Polymers with Cleavage-Induced Phase Transition Reviewed

    Yukiya Kitayama, Yasumichi Yazaki, Junya Emoto, Eiji Yuba, Atsushi Harada

    Molecules   27 ( 18 )   6082   2022.09

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    DOI: 10.3390/molecules27186082

    PubMed

  • Plant lectins and their usage in preparing targeted nanovaccines for cancer immunotherapy Reviewed International coauthorship

    Bhavika Gupta, Daizy Sadaria, Vaishnavi U. Warrier, Anuradha Kirtonia, Ravi Kant, Amit Awasthi, Prakash Baligar, Jayanta K. Pal, Eiji Yuba, Gautam Sethi, Manoj Garg, Rajesh Kumar Gupta

    Seminars in Cancer Biology   80   87 - 106   2022.05( ISSN:1044-579X

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    DOI: 10.1016/j.semcancer.2020.02.005

    PubMed

  • Potent adjuvant effect elicited for tumor immunotherapy by a liposome conjugated pH-sensitive polymer and dendritic cell-targeting Toll-like-receptor ligand Reviewed

    Shunichi Watanabe, Eiji Yuba, Takashi Akazawa, Viskam Wijewardana, Yuka Kakihara, Ayaka Azuma, Kenji Hagimori, Ryoji Kanegi, Shingo Hatoya, Norimitsu Inoue, Toshio Inaba, Kikuya Sugiura

    Vaccine   40 ( 10 )   1448 - 1457   2022.02( ISSN:0264-410X

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    Authorship:Lead author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    The generation of DCs with augmented functions is a strategy for obtaining satisfactory clinical outcomes in tumor immunotherapy. We developed a novel synthetic adjuvant comprising a liposome conjugated with a DC-targeting Toll-like-receptor ligand and a pH-sensitive polymer for augmenting cross-presentation. In an in vitro study using mouse DCs, these liposomes were selectively incorporated into DCs, significantly enhanced DC function and activated immune responses to present an epitope of the incorporated antigen on the major histocompatibility complex class I molecules. Immunization of mice with liposomes encapsulating a tumor antigen significantly enhanced antigen-specific cytotoxicity. In tumor-bearing mice, vaccination with liposomes encapsulating a tumor antigen elicited complete tumor remission. Furthermore, vaccination significantly enhanced cytotoxicity, targeting not only the vaccinated antigen but also the other antigens of the tumor cell. These results indicate that liposomes are an ideal adjuvant to develop DCs with considerably high potential to elicit antigen-specific immune responses; they are a promising tool for cancer therapy with neoantigen vaccination.

    DOI: 10.1016/j.vaccine.2022.01.048

    PubMed

  • Engineered collagen-targeting therapeutics reverse lung and kidney fibrosis in mice Reviewed International coauthorship

    Michael JV White, Michal M Raczy, Erica Budina, Eiji Yuba, Ani Solanki, Ha-Na Shim, Zheng Jenny Zhang, Laura T Gray, Shijie Cao, Aaron T. Alpar, Jeffrey A Hubbell

    bioRxiv   2022.01

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Abstract

    Fibrotic diseases are involved in 45% of deaths in the United States. In particular, fibrosis of the kidney and lung are major public health concerns due to their high prevalence and lack of existing treatment options. Here, we harness the pathophysiological features of fibrotic diseases, namely leaky vasculature and aberrant extracellular matrix (ECM) protein deposition (i.e. collagen), to target an anti-fibrotic biologic and a small molecule drug to disease sites of fibrosis, thus improving their therapeutic potential in mouse models of lung and kidney fibrosis. First, we identify and validate collagen-targeting drug delivery systems that preferentially accumulate in the diseased organs: von Willebrand Factor’s A3 domain (VWF-A3) and decorin-derived collagen-binding peptide-conjugated micelles (CBP-micelles). We then engineer and recombinantly express novel candidate biologic therapies based on the anti-inflammatory cytokine IL-10: A3-IL-10 and A3-Serum Albumin-IL-10 (A3-SA-IL-10). Simultaneously, we stably encapsulate the potential anti-fibrotic water-insoluble drug, rapamycin, in CBP-micelles. We show that these novel formulations of therapeutics bind to collagen in vitro and that their efficacy in mouse models of lung and kidney fibrosis is improved, compared to free, untargeted drugs. Our results demonstrate that collagen-targeted anti-fibrotic drugs may be next generation therapies of high clinical potential.

    DOI: 10.1101/2022.01.04.474747

  • 腫瘍免疫活性化のためのポリカルボン酸結合抗体の創製

    弓場 英司

    上原記念生命科学財団研究報告集   35   1 - 5   2021.12

  • pH-Sensitive branched β-glucan-modified liposomes for activation of antigen presenting cells and induction of antitumor immunity. Invited Reviewed

    Shin Yanagihara, Nozomi Kasho, Koichi Sasaki, Naoto Shironaka, Yukiya Kitayama, Eiji Yuba, Atsushi Harada

    Journal of materials chemistry. B   9 ( 37 )   7713 - 7724   2021.09

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Induction of cellular immunity is important for effective cancer immunotherapy. Although various antigen carriers for cancer immunotherapy have been developed to date, balancing efficient antigen delivery to antigen presenting cells (APCs) and their activation via innate immune receptors, both of which are crucially important for the induction of strong cellular immunity, remains challenging. For this study, branched β-glucan was selected as an intrinsically immunity-stimulating and biocompatible material. It was engineered to develop multifunctional liposomal cancer vaccines capable of efficient interactions with APCs and subsequent activation of the cells. Hydroxy groups of branched β-glucan (Aquaβ) were modified with 3-methylglutaric acid ester and decyl groups, respectively, to provide pH-sensitivity and anchoring capability to the liposomal membrane. The modification efficiency of Aquaβ derivatives to the liposomes was significantly high compared with linear β-glucan (curdlan) derivatives. Aquaβ derivative-modified liposomes released their contents in response to weakly acidic pH. As a model antigenic protein, ovalbumin (OVA)-loaded liposomes modified with Aquaβ derivatives interacted efficiently with dendritic cells, and induced inflammatory cytokine secretion from the cells. Subcutaneous administration of Aquaβ derivative-modified liposomes suppressed the growth of the E.G7-OVA tumor significantly compared with curdlan derivative-modified liposomes. Aquaβ derivative-modified liposomes induced the increase of CD8+ T cells, and polarized macrophages to the antitumor M1-phenotype within the tumor microenvironment. Therefore, pH-sensitive Aquaβ derivatives can be promising materials for liposomal antigen delivery systems to induce antitumor immune responses efficiently.

    DOI: 10.1039/d1tb00786f

    PubMed

  • Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery. Reviewed International coauthorship

    Kosuke Noguchi, Momoko Obuki, Haruka Sumi, Merlin Klußmann, Kenta Morimoto, Shinya Nakai, Takuya Hashimoto, Daisuke Fujiwara, Ikuo Fujii, Eiji Yuba, Tomoka Takatani-Nakase, Ines Neundorf, Ikuhiko Nakase

    Molecular pharmaceutics   18 ( 9 )   3290 - 3301   2021.08

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    The antimicrobial protein CAP18 (approximate molecular weight: 18 000), which was first isolated from rabbit granulocytes, comprises a C-terminal fragment that has negatively charged lipopolysaccharide binding activity. In this study, we found that CAP18 (106-121)-derived (sC18)2 peptides have macropinocytosis-inducible biological functions. In addition, we found that these peptides are highly applicable for use as extracellular vesicle (exosomes, EV)-based intracellular delivery, which is expected to be a next-generation drug delivery carrier. Here, we demonstrate that dimerized (sC18)2 peptides can be easily introduced on EV membranes when modified with a hydrophobic moiety, and that they show high potential for enhanced cellular uptake of EVs. By glycosaminoglycan-dependent induction of macropinocytosis, cellular EV uptake in targeted cells was strongly increased by the peptide modification made to EVs, and intriguingly, our herein presented technique is efficiently applicable for the cytosolic delivery of the biologically cell-killing functional toxin protein, saporin, which was artificially encapsulated in the EVs by electroporation, suggesting a useful technique for EV-based intracellular delivery of biofunctional molecules.

    DOI: 10.1021/acs.molpharmaceut.1c00244

    PubMed

  • Multifunctional Traceable Liposomes with Temperature-Triggered Drug Release and Neovasculature-Targeting Properties for Improved Cancer Chemotherapy. Reviewed International coauthorship

    Eiji Yuba, Munenobu Takashima, Takaaki Hayashi, Daisuke Kokuryo, Ichio Aoki, Atsushi Harada, Sadahito Aoshima, Uma Maheswari Krishnan, Kenji Kono

    Molecular pharmaceutics   18 ( 9 )   3342 - 3351   2021.07

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Poor distribution of nanocarriers at the tumor site and insufficient drug penetration into the tissue are major challenges in the development of effective and safe cancer therapy. Here, we aim to enhance the therapeutic effect of liposomes by accumulating doxorubicin-loaded liposomes at high concentrations in and around the tumor, followed by heat-triggered drug release to facilitate low-molecular-weight drug penetration throughout the tumor. A cyclic RGD peptide (cRGD) was incorporated into liposomes decorated with a thermosensitive polymer that allowed precise tuning of drug release temperature (i.e., Polymer-lip) to develop a targeted thermosensitive liposome (cRGD-Polymer-lip). Compared with conventional thermosensitive liposomes, cRGD-Polymer-lip enhanced the binding of liposomes to endothelial cells, leading to their accumulation at the tumor site upon intravenous administration in tumor-bearing mice. Drug release triggered by local heating strongly inhibited tumor growth. Notably, tumor remission was achieved via multiple administrations of cRGD-Polymer-lip and heat treatments. Thus, combining the advantages of tumor neovascular targeting and heat-triggered drug release, these liposomes offer high potential for minimally invasive and effective cancer chemotherapy.

    DOI: 10.1021/acs.molpharmaceut.1c00263

    PubMed

  • Prolonged residence of an albumin–IL-4 fusion protein in secondary lymphoid organs ameliorates experimental autoimmune encephalomyelitis Reviewed International coauthorship

    Ako Ishihara, Jun Ishihara, Elyse A. Watkins, Andrew C. Tremain, Mindy Nguyen, Ani Solanki, Kiyomitsu Katsumata, Aslan Mansurov, Erica Budina, Aaron T. Alpar, Peyman Hosseinchi, Lea Maillat, Joseph W. Reda, Takahiro Kageyama, Melody A. Swartz, Eiji Yuba, Jeffrey A. Hubbell

    Nature Biomedical Engineering   5 ( 5 )   387 - 398   2021.05

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Interleukin-4 (IL-4) suppresses the development of multiple sclerosis in a murine model of experimental autoimmune encephalomyelitis (EAE). Here, we show that, in mice with EAE, the accumulation and persistence in the lymph nodes and spleen of a systemically administered serum albumin (SA)-IL-4 fusion protein leads to higher efficacy in preventing disease development than the administration of wild-type IL-4 or of the clinically approved drug fingolimod. We also show that the SA-IL-4 fusion protein prevents immune-cell infiltration in the spinal cord, decreases integrin expression in antigen-specific CD4+ T cells, increases the number of granulocyte-like myeloid-derived suppressor cells (and their expression of programmed-death-ligand-1) in spinal cord-draining lymph nodes and decreases the number of T helper 17 cells, a pathogenic cell population in EAE. In mice with chronic EAE, SA-IL-4 inhibits immune-cell infiltration into the spinal cord and completely abrogates immune responses to myelin antigen in the spleen. The SA-IL-4 fusion protein may be prophylactically and therapeutically advantageous in the treatment of multiple sclerosis.

    DOI: 10.1038/s41551-020-00627-3

    PubMed

    Other URL: http://www.nature.com/articles/s41551-020-00627-3

  • Suppression of Rheumatoid Arthritis by Enhanced Lymph Node Trafficking of Engineered Interleukin‐10 in Murine Models Reviewed International coauthorship

    Eiji Yuba, Erica Budina, Kiyomitsu Katsumata, Ako Ishihara, Aslan Mansurov, Aaron T. Alpar, Elyse A. Watkins, Peyman Hosseinchi, Joseph W. Reda, Abigail L. Lauterbach, Mindy Nguyen, Ani Solanki, Takahiro Kageyama, Melody A. Swartz, Jun Ishihara, Jeffrey A. Hubbell

    Arthritis & Rheumatology   73 ( 5 )   769 - 778   2021.05( ISSN:2326-5191

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    Authorship:Lead author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    OBJECTIVE: Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials have been performed using interleukin-10 (IL-10), an antiinflammatory cytokine, as a potential treatment of RA, the therapeutic effects of IL-10 have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. This study was undertaken to engineer an IL-10-serum albumin (SA) fusion protein and evaluate its effects in 2 murine models of RA. METHODS: SA-fused IL-10 (SA-IL-10) was recombinantly expressed. Mice with collagen antibody-induced arthritis (n = 4-7 per group) or collagen-induced arthritis (n = 9-15 per group) were injected intravenously with wild-type IL-10 or SA-IL-10, and the retention of SA-IL-10 in the lymph nodes (LNs), immune cell composition in the paws, and therapeutic effect of SA-IL-10 on mice with arthritis were assessed. RESULTS: SA fusion to IL-10 led to enhanced accumulation in the mouse LNs compared with unmodified IL-10. Intravenous SA-IL-10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive alternatively activated macrophages, reduced IL-17A levels in the paw-draining LN, and protected joint morphology. Intravenous SA-IL-10 treatment showed similar efficacy as treatment with an anti-tumor necrosis factor antibody. SA-IL-10 was equally effective when administered intravenously, locally, or subcutaneously, which is a benefit for clinical translation of this molecule. CONCLUSION: SA fusion to IL-10 is a simple but effective engineering strategy for RA therapy and has potential for clinical translation.

    DOI: 10.1002/art.41585

    PubMed

    Other URL: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/art.41585

  • Carboxylated polyamidoamine dendron-bearing lipid-based assemblies for precise control of intracellular fate of cargo and induction of antigen-specific immune responses Reviewed

    Eiji Yuba, Yoshikatsu Sugahara, Yuta Yoshizaki, Takeyuki Shimizu, Michiyuki Kasai, Keiko Udaka, Kenji Kono

    Biomaterials Science   9 ( 8 )   3076 - 3089   2021.04( ISSN:2047-4830

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    For the establishment of advanced medicines such as cancer immunotherapy, high performance carriers that precisely deliver biologically active molecules must be developed to target organelles of the cells and to release their contents there. From the viewpoint of antigen delivery, endosomes are important target organelles because they contain immune-response-related receptors and proteins of various types. To obtain carriers for precision endosome delivery, a novel type of polyamidoamine dendron-based lipid having pH-sensitive terminal groups was synthesized for this study. Liposomes were prepared using these pH-sensitive dendron-based lipids and egg yolk phosphatidylcholine. Their pH-responsive properties and performance as an endosome delivery carrier were investigated. pH-Sensitive dendron lipid-based liposomes retained water-soluble molecules at neutral pH but released them under weakly acidic conditions. Particularly, liposomes containing CHexDL-G1U exhibited highly sensitive properties responding to very weakly acidic pH. These dendron lipid-based liposomes released the contents specifically in the endosome. The timing of content release can be controlled by selecting pH-sensitive dendron lipids for liposome preparation. Significant tumor regression was induced in tumor-bearing mice by the administration of CHexDL-G1U-modified liposomes containing the model antigenic protein. Furthermore, CHexDL-G1U-modified liposomes induced WT1 tumor antigenic peptide-specific helper T cell proliferation. The results demonstrate that dendron lipid-based liposomes are useful as a potent vaccine for cancer immunotherapy.

    DOI: 10.1039/d0bm01813a

    PubMed

  • Fabrication of gold nanohybrids modified with antibody and functional dendrimers for targeted photothermal theranostics Reviewed

    Herlan Setiawan, Eiji Yuba, Atsushi Harada, Ichio Aoki, Kenji Kono

    Nano Select   2 ( 4 )   779 - 790   2021.04( ISSN:2688-4011

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    DOI: 10.1002/nano.202000218

    Other URL: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/nano.202000218

  • Hydrophilic Hyperbranched Polymer-Coated siRNA/Polyamidoamine Dendron-Bearing Lipid Complexes Preparation for High Colloidal Stability and Efficient RNAi Reviewed

    Eiji Yuba, Takashi Korenaga, Atsushi Harada

    Bioconjugate Chemistry   32 ( 3 )   563 - 571   2021.03( ISSN:1043-1802

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    RNA interference (RNAi) using siRNA has gained much attention for use in therapies for cancer and genetic disorders. To establish RNAi-based therapeutics, the development of efficient siRNA nanocarriers is desired. Earlier, we developed polyamidoamine dendron-bearing lipids able to form complexes with nucleic acids as gene vectors. Especially, dendron lipids with unsaturated alkyl chains (DL-G1-U2) induced efficient endosomal escape by membrane fusion, leading to efficient transfection in vitro. For this study, dendron lipids having oleyl/linoleyl groups (DL-G1-U3) were designed to increase membrane fusogenic activity further. Indeed, DL-G1-U3/siRNA complexes achieved higher membrane fusogenic activity and knockdown of the target gene more efficiently than conventional DL-G1-U2/siRNA complexes did. A hydrophilic polymer, hyperbranched polyglycidol lauryl ester (HPG-Lau), was modified further on the surface of DL-G1-U3/siRNA complexes to provide colloidal stability. Surface modification of HPG-Lau increased the colloidal stability in a physiological condition more than complexes without HPG-Lau. Importantly, HPG-Lau-coated DL/siRNA complexes showed identical RNAi effects to those of parental DL/siRNA complexes, whereas the RNAi activity of poly(ethylene glycol)-bearing lipid (PEG-PE)-modified DL/siRNA complexes was hindered completely. Introduction of unsaturated bonds into dendron lipids and selection of suitable hydrophilic polymers for nanocarrier modification are important for obtaining efficient siRNA vectors toward in vivo siRNA delivery.

    DOI: 10.1021/acs.bioconjchem.1c00035

    PubMed

  • Environmental pH stress influences cellular secretion and uptake of extracellular vesicles Reviewed International coauthorship

    Ikuhiko Nakase, Natsumi Ueno, Mie Matsuzawa, Kosuke Noguchi, Mami Hirano, Mika Omura, Tomoya Takenaka, Ayaka Sugiyama, Nahoko Bailey Kobayashi, Takuya Hashimoto, Tomoka Takatani‐Nakase, Eiji Yuba, Ikuo Fujii, Shiroh Futaki, Tetsuhiko Yoshida

    FEBS Open Bio   11 ( 3 )   753 - 767   2021.03( ISSN:2211-5463

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Exosomes (extracellular vesicles/EVs) participate in cell–cell communication and contain bioactive molecules, such as microRNAs. However, the detailed characteristics of secreted EVs produced by cells grown under low pH conditions are still unknown. Here, we report that low pH in the cell culture medium significantly affected the secretion of EVs with increased protein content and zeta potential. The intracellular expression level and location of stably expressed GFP-fused CD63 (an EV tetraspanin) in HeLa cells were also significantly affected by environmental pH. In addition, increased cellular uptake of EVs was observed. Moreover, the uptake rate was influenced by the presence of serum in the cell culture medium. Our findings contribute to our understanding of the effect of environmental conditions on EV-based cell–cell communication.

    DOI: 10.1002/2211-5463.13107

    PubMed

    Other URL: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/2211-5463.13107

  • Development of mannose-modified carboxylated curdlan-coated liposomes for antigen presenting cell targeted antigen delivery Invited Reviewed

    Eiji Yuba, Yoshiki Fukaya, Shin Yanagihara, Nozomi Kasho, Atsushi Harada

    Pharmaceutics   12 ( 8 )   1 - 14   2020.08

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    Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity.

    DOI: 10.3390/pharmaceutics12080754

    PubMed

  • Light-activatable transfection system using hybrid vectors composed of thermosensitive dendron lipids and gold nanorods Reviewed

    Takuya Hashimoto, Tomoya Hirata, Eiji Yuba, Atsushi Harada, Kenji Kono

    Pharmaceutics   12 ( 3 )   2020.03

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    Background: Gene delivery to target cells is crucially important to establish gene therapy and regenerative medicine. Although various virus-based and synthetic molecule-based gene vectors have been developed to date, selective transfection in a site or a cell level is still challenging. For this study, both light-responsive and temperature-responsive synthetic gene vectors were designed for spatiotemporal control of a transfection system. Methods: 11-Mercaptoundecanoic acid-coated gold nanorods were mixed with polyamidoamine dendron-bearing lipids of two types having amino-terminus or ethoxydiethylene glycol-terminus to obtain hybrid vectors. Hybrid vectors were mixed further with pDNA. Then we investigated their physicochemical properties and transfection efficacy with or without near infrared laser irradiation. Results: Hybrid vectors formed complexes with pDNA and exhibited enhanced photothermal property under near infrared laser irradiation compared with parent gold nanorods. Transfection efficacy of complexes was promoted considerably by brief laser irradiation soon after complex application to the cells. Analysis of intracellular distribution revealed that laser irradiation promoted the adsorption of complexes to the cells and cytosolic release of pDNA, which is derived from the change in surface hydrophobicity of complexes through dehydration of temperature-responsive groups. Conclusions: Hybrid vector is promising as a light-activatable transfection system.

    DOI: 10.3390/pharmaceutics12030239

    PubMed

  • Temperature-responsive molecular assemblies using oligo(ethylene glycol)-attached polyamidoamine dendron lipids and their functions as drug carriers Reviewed

    Takuya Hashimoto, Yuji Hirai, Eiji Yuba, Atsushi Harada, Kenji Kono

    Journal of Functional Biomaterials   11 ( 1 )   2020.03

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    Temperature-responsive nanocarrier systems using external stimuli are one of the most widely investigated stimuli-responsive strategies because heat is easy and safe to use for hyperthermia and controlled drug delivery. Polyamidoamine dendron lipids (PAMAM-DLs) composed of PAMAM dendron as head group and two alkyl chains can exhibit temperature-responsive morphological change through the attachment of suitable moieties to terminal of PAMAM dendron. In this study, oligo(ethylene glycol)s including ethoxy- or methoxy-diethylene glycols were attached to the terminals of PAMAM-DL, and temperature-responsive properties of their self-assemblies were evaluated by calorimetric and turbidity measurements. In the evaluation of temperature-responsive properties, ethoxy diethylene glycol (EDEG)-attached PAMAM-DL composed of two saturated alkyl chains and PAMAM dendron with 1st generation had lipid bilayer structure and suitable cloud point for the application as drug carrier. In vitro performances of the assemblies combining EDEG-attached PAMAM-DLs with cholesteryl-oxy-poly(ethylene glycol) (PEG-Chol) was evaluated using doxorubicin (DOX) as an anticancer drug. Cellular uptake of DOX-loaded EDEG-attached PAMAM-DL/PEG-Chol assemblies was promoted at 42 ◦C rather than 37 ◦C, resulting in an effective decrease in cell viability.

    DOI: 10.3390/jfb11010016

    PubMed

  • Preparation of photothermal-chemotherapy nanohybrids by complexation of gold nanorods with polyamidoamine dendrimers having poly(ethylene glycol) and hydrophobic chains Reviewed

    Takuya Hashimoto, Eiji Yuba, Atsushi Harada, Kenji Kono

    Journal of Materials Chemistry B   8 ( 14 )   2826 - 2833   2020.03( ISSN:2050-750X

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Functional dendrimer-gold nanorod hybrid for combination of anticancer drugs and laser hyperthermia towards efficient cancer treatment with less-adverse effects.

    DOI: 10.1039/c9tb02163a

    PubMed

  • Development of functional liposomes by modification of stimuli-responsive materials and their biomedical applications Reviewed

    Eiji Yuba

    Journal of Materials Chemistry B   8 ( 6 )   1093 - 1107   2020.02( ISSN:2050-750X

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    Authorship:Lead author, Last author, Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Liposomes are a promising nanocarrier for drug delivery because of their biocompatibility and the encapsulation capacity of drugs. Liposomes can be functionalized easily by introduction of functional materials such as stimulus-responsive materials. Temperature-responsive liposomes and pH-responsive liposomes are representative stimulus-responsive liposomes that can deliver drugs to locally heated target tissues and intracellular organelles. Here, temperature-responsive liposomes for the selective release of cargo and pH-responsive liposomes for the induction of antigen-specific immunity are overviewed. Temperature-responsive polymer-modified liposomes immediately released drugs in response to heating, which achieved selective drug release at a tumour after topical heating of tumour-bearing mice. Introduction of MR-detectable molecules enabled the tracing of liposome accumulation into target sites to optimize the heating timing. These liposomes can also be combined with magnetic nanoparticles or carbon nanomaterials to attain magnetic field-responsive, electric field-responsive and light-responsive properties to support on-demand drug release or control of biological reactions using these external stimuli. pH-Responsive liposomes were produced by modification of poly(carboxylic acid) derivatives or by pH-responsive amphiphiles. These liposomes delivered antigenic proteins into the cytosol of antigen presenting cells, which induced cross-presentation and antigen-specific cellular immunity. Adjuvant molecules or bioactive polysaccharide-based pH-responsive polymers improved their immunity-inducing effect further, leading to tumour regression in tumour-bearing mice. Precise design and control of the structures of stimulus-responsive materials and combination with functional materials are expected to create novel methodologies to control biological functions and to produce highly potent liposomal drugs that can achieve selective release of bioactive molecules.

    DOI: 10.1039/c9tb02470k

    PubMed

  • Manipulation of the tumor microenvironment by cytokine gene transfection enhances dendritic cell-based immunotherapy Reviewed

    Daluthgamage Patsy Himali Wijesekera, Eiji Yuba, Nadeeka Harshini De Silva, Shun ichi Watanabe, Masaya Tsukamoto, Chihiro Ichida, Takeshi Izawa, Kazuyuki Itoh, Ryoji Kanegi, Shingo Hatoya, Jyoji Yamate, Toshio Inaba, Kikuya Sugiura

    FASEB BioAdvances   2 ( 1 )   5 - 17   2020.01

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    The tumor microenvironment strongly influences clinical outcomes of immunotherapy. By transfecting genes of relevant cytokines into tumor cells, we sought to manipulate the microenvironment so as to elicit activation of T helper type 1 (Th1) responses and the maturation of dendritic cells (DCs). Using a synthetic vehicle, the efficiency of in vivo transfection of GFP-cDNA into tumor cells was about 7.5% by intratumoral injection and about 11.5% by intravenous injection. Survival was significantly improved by both intratumoral and intravenous injection of the plasmid containing cDNA of interferon-gamma, followed by intratumoral injection of DCs presenting the tumor antigens. Also, tumor growth was inhibited by these treatments. A more significant effect on survival and tumor growth inhibition was observed following injection of the plasmid containing cDNA of CD40 ligand, which is a potent inducer of DC-maturation. Furthermore, the co-injection of both IFNγ- and CD40 ligand-encoding cDNA-plasmids, followed by DC treatment, gave rise to further marked and enhancement, including 100% survival and more than 50% complete remission. This treatment regimen elicited significant increases in mature DCs and types of cells contributing to Th1 responses, and significant decreases in immune suppressor cells in the tumor. In the spleen, the treatment significantly increased activities of tumor-specific killer and natural killer cells, but no alteration was observed in mature DCs or suppressor cells. These results indicate that transfection of these cytokine genes into tumor cells significantly alter the tumor microenvironment and improve the therapeutic results of DC-based immunotherapy.

    DOI: 10.1096/fba.2019-00052

    PubMed

  • Comparison of in Vitro Performances of Nanorod and Nanofiber Polyplexes Prepared from Plasmid DNA and Poly(L-lysine) Terminally Bearing Multi-Arm PEG Reviewed

    Ryuta Aono, Kenta Nomura, Eiji Yuba, Atsushi Harada

    ACS Symposium Series   1350   13 - 21   2020( ISSN:0097-6156

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    Publishing type:Part of collection (book)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Poly(L-lysine)-bearing multi-arm poly(ethylene glycol) terminary (maPEG-PLL) can form nanorod and nanofiber polyplexes with plasmid DNA (pDNA) depending on the size (exclusion volume) of maPEG. Nanorod and nanofiber polyplexes were prepared using maPEG-PLL bearing different maPEG sizes. Gene expression of nanofiber and nanorod polyplexes was comparable, although the cellular uptake of nanofiber polyplexes was less than that of nanorod polyplexes. This suggests that there is a difference in cellular activities after polyplex enters the cell. The release of pDNA from polyplexes through the exchange with heparin occurred more easily in nanorod polyplexes than it did in nanofiber polyplexes. However, it was confirmed by real-time PCR measurements that pDNA molecules in nanofiber polyplexes exhibit high reactivity with polymerase compared with that in nanorod polyplexes. Further, higher reactivity of pDNA with polymerase in nanofiber polyplexes was maintained even in the presence of crowding cosolutes including Ficoll and dextran. This suggests that pDNA in nanofiber polyplex might reflect a higher efficiency of transcription process in the cell compared with pDNA in nanorod polyplex. These results provide valuable information in the design of nonviral gene vectors using cationic polymers.

    DOI: 10.1021/bk-2020-1350.ch002

  • Conferring extracellular matrix affinity enhances local therapeutic efficacy of anti-TNF-α antibody in a murine model of rheumatoid arthritis Reviewed International coauthorship

    Kiyomitsu Katsumata, Jun Ishihara, Kazuto Fukunaga, Ako Ishihara, Eiji Yuba, Erica Budina, Jeffrey A. Hubbell

    Arthritis Research and Therapy   21 ( 1 )   298 - 298   2019.12( ISSN:1478-6354

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Background: Although disease in a majority of rheumatoid arthritis (RA) patients is often initially limited to one or a few joints, currently approved medications including anti-tumor necrosis factor-α antibody (α-TNF) are injected systemically. Given that α-TNF systemic injection typically does not cure RA and involves risk of treatment-related adverse events, one possible approach to enhance therapeutic efficacy and reduce α-TNF systemic exposure is to retain the antibodies in arthritic joints after local administration. The aim of this study was to evaluate the approach of conferring extracellular matrix (ECM) binding affinity to α-TNF antibodies in a RA model. Methods: α-TNF was chemically conjugated with a promiscuous ECM-binding peptide derived from placenta growth factor 2 (PlGF-2123-144). The binding activity of PlGF-2123-144-conjugated α-TNF (PlGF-2123-144-α-TNF) against ECM proteins was assessed by ELISA and by immunostaining on human cartilage specimens. The effect of conjugation on antibody function was assessed as a neutralizing activity against osteoclast differentiation. Retention at the injection site and therapeutic efficacy of PlGF-2123-144-α-TNF were tested in a collagen antibody-induced arthritis (CAIA) model in the mouse. Results: PlGF-2123-144 peptide conjugation conferred α-TNF with affinity to ECM proteins without impairment of antigen recognition. PlGF-2123-144-α-TNF locally injected at a paw in the CAIA model was retained for at least 96 h at the injection site, whereas unmodified α-TNF was dispersed rapidly after injection. Local treatment with unmodified α-TNF did not suppress the arthritis score relative to isotype controls. By contrast, local administration of PlGF-2123-144-α-TNF suppressed arthritis development almost completely in the treated paw even at a 1000× lower dose. Conclusion: These data demonstrate that retention of α-TNF in arthritic joints can suppress arthritis development and enhance therapeutic efficacy. This simple bioengineering approach of ECM-binding peptide conjugation offers a powerful and clinically translational approach to treat RA.

    DOI: 10.1186/s13075-019-2075-8

    PubMed

  • Effects of Lyophilization of Arginine-rich Cell-penetrating Peptide-modified Extracellular Vesicles on Intracellular Delivery. Reviewed

    Kosuke Noguchi, Mami Hirano, Takuya Hashimoto, Eiji Yuba, Tomoka Takatani-Nakase, Ikuhiko Nakase

    Anticancer research   39 ( 12 )   6701 - 6709   2019.12

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    BACKGROUND/AIM: Extracellular vesicles (exosomes, EVs) (30-200 nm in diameter) are secreted by various cells in the body. Owing to the pharmaceutical advantages of EVs, an EV-based drug delivery system (DDS) for cancer therapy is expected to be the next-generation therapeutic system. However, preservation methods for functional and therapeutic EVs should be developed. Here, we developed the method of lyophilization of arginine-rich cell penetrating peptide (CPP)-modified EVs and investigated the effects of lyophilization on the characteristics of EVs. MATERIALS AND METHODS: Particle size, structure, zeta-potential, and cellular uptake efficacy of the arginine-rich CPP-modified EVs were analyzed. The model protein saporin (SAP), having anti-cancer effects, was encapsulated inside the EVs to assess the cytosolic release of EV content after cellular uptake. RESULTS: Lyophilization of the EVs did not affect their particle size, structure, zeta-potential, and cellular uptake efficacy; however, the biological activity of the encapsulated SAP was inhibited by lyophilization. CONCLUSION: Lyophilization of EVs may affect SAP structures and/or reduce the cytosolic release efficacy of EV's content after cellular uptake and needs attention in EV-based DDSs.

    DOI: 10.21873/anticanres.13885

    PubMed

  • Development of pH-Responsive Hyaluronic Acid-Based Antigen Carriers for Induction of Antigen-Specific Cellular Immune Responses Invited Reviewed

    Maiko Miyazaki, Eiji Yuba, Hiroshi Hayashi, Atsushi Harada, Kenji Kono

    ACS Biomaterials Science and Engineering   5 ( 11 )   5790 - 5797   2019.11

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Cancer immunotherapy has gained much attention because of the recent success of immune checkpoint inhibitors. Nevertheless, clinical therapeutic effects of immune checkpoint inhibitors remain limited, probably because most patients have other immune checkpoint molecules or because they lack cancer-specific cytotoxic T lymphocytes. Induction of cancer-specific cytotoxic T lymphocytes requires efficient antigen delivery systems that can convey cancer antigens specifically to antigen presenting cells, promote the endosomal escape of antigen into cytosol, and activate immune cells. Earlier, we reported cytoplasmic delivery systems of antigen using pH-sensitive polymer-modified liposomes. Adjuvant molecules were further incorporated into these liposomes to provide activation properties of cellular immune responses. This study further introduced cell specificity to these liposomal systems using hyaluronic acid-based pH-sensitive polymers, which are recognized by CD44 expressing on antigen presenting cells. pH-Sensitive hyaluronic acid derivative-modified liposomes showed much higher cellular association to antigen presenting cells than to fibroblasts with less CD44 expression. These liposomes achieved the delivery of model antigenic proteins into cytosol of dendritic cells and promoted Th1 cytokine production from the cells. Subcutaneous administration of these liposomes to mice induced antigen-specific cellular immune response in the spleen, leading to tumor regression in tumor-bearing mice. The results show that pH-sensitive hyaluronic acid derivative-modified liposomes are promising as multifunctional antigen carriers having cell-specificity, cytoplasmic antigen delivery performance, and adjuvant property to induce antigen-specific cellular immunity.

    DOI: 10.1021/acsbiomaterials.9b01278

    PubMed

  • Gene Expression of Aspect Ratio-Controlled Polyplexes Based on the Effect of Multi-Arm Poly(ethylene glycol) Reviewed

    Atsushi Harada, Kenta Nomura, Eiji Yuba, Kenji Kono

    ACS Biomaterials Science and Engineering   5 ( 11 )   5681 - 5687   2019.11

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    Controlling the aspect ratio of polyplexes prepared by mixing pDNA with a polycation mixture of a poly(l-lysine) (PLL) homopolymer and PLL terminally bearing a multiarm poly(ethylene glycol) (PEG) part (maPEG-PLL) was examined. By varying the maPEG-PLL content in the polycation mixture, the condensation of pDNA accompanied by polyplex formation and the morphology of the polyplexes were evaluated by a dye exclusion assay and AFM observations, respectively. Increasing the maPEG-PLL content caused elongation of the polyplex, and polyplexes with aspect ratios from 2 to 10 were prepared successfully by controlling the maPEG-PLL content. The reactivity of pDNA in the polyplexes with varying aspect ratios against DNase I and polymerase were examined by agarose gel electrophoresis and real-time PCR measurements, respectively. Moreover, cellular uptake and transfection efficiency of the polyplexes by HeLa cells was evaluated. The results revealed that an increase in aspect ratio of the polyplexes caused an increase in PCR efficiency with a concomitant decrease in cellular uptake.

    DOI: 10.1021/acsbiomaterials.8b01498

    PubMed

  • Targeting inflammatory sites through collagen affinity enhances the therapeutic efficacy of anti-inflammatory antibodies Reviewed International coauthorship

    Kiyomitsu Katsumata, Jun Ishihara, Aslan Mansurov, Ako Ishihara, Michal M. Raczy, Eiji Yuba, Jeffrey A. Hubbell

    Science Advances   5 ( 11 )   eaay1971   2019.11

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    Enhancing the therapeutic efficacy of drugs for inflammatory diseases is of high demand. One possible approach is targeting drugs to the extracellular matrix of the inflamed area. Here, we target collagens in the matrix, which are inaccessible in most tissues yet are exposed to the bloodstream in the inflamed area because of vascular hyperpermeability. We conferred collagen affinity to anti–tumor necrosis factor-α (α-TNF) antibody by conjugating a collagen-binding peptide (CBP) derived from the sequence of decorin. CBP–α-TNF accumulated in the inflamed paw of the arthritis model, and arthritis development was significantly suppressed by treatment with CBP–α-TNF compared with the unmodified antibody. Similarly, CBP–anti-transforming growth factor-β (α–TGF-β) accumulated in the inflamed lung of pulmonary fibrosis model and significantly suppressed pulmonary fibrosis compared with the unmodified antibody. Together, collagen affinity enables the anticytokine antibodies to target arthritis and pulmonary fibrosis accompanied by inflammation, demonstrating a clinically translational approach to treat inflammatory diseases.

    DOI: 10.1126/sciadv.aay1971

    PubMed

  • Engineering anti-cancer nanovaccine based on antigen cross-presentation Reviewed International coauthorship

    Vaishnavi U. Warrier, Amina I. Makandar, Manoj Garg, Gautam Sethi, Ravi Kant, Jayanta K. Pal, Eiji Yuba, Rajesh Kumar Gupta

    Bioscience Reports   39 ( 10 )   2019.10( ISSN:0144-8463

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    Dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules, thereby activating CD8+ T cells, contributing to tumor elimination through a mechanism known as antigen cross-presentation. A variety of factors such as maturation state of DCs, co-stimulatory signals, T-cell microenvironment, antigen internalization routes and adjuvants regulate the process of DC-mediated antigen cross-presentation. Recently, the development of successful cancer immunotherapies may be attributed to the ability of DCs to cross-present tumor antigens. In this review article, we focus on the underlying mechanism of antigen cross-presentation and ways to improve antigen cross-presentation in different DC subsets. We have critically summarized the recent developments in the generation of novel nanovaccines for robust CD8+ T-cell response in cancer. In this context, we have reviewed nanocarriers that have been used for cancer immunotherapeutics based on antigen cross-presentation mechanism. Additionally, we have also expressed our views on the future applications of this mechanism in curing cancer.

    DOI: 10.1042/BSR20193220

    PubMed

  • Chondroitin Sulfate-Based pH-Sensitive Polymer-Modified Liposomes for Intracellular Antigen Delivery and Induction of Cancer Immunity. Reviewed

    Minori Okubo, Maiko Miyazaki, Eiji Yuba, Atsushi Harada

    Bioconjugate chemistry   30 ( 5 )   1518 - 1529   2019.05( ISSN:1043-1802

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Induction of cancer-specific cytotoxic T lymphocytes is crucially important to complement therapeutic effects of immune checkpoint inhibitors and to achieve efficient cancer immunotherapy. To induce cancer-specific cytotoxic T lymphocytes, cancer antigen carriers must have multiple functions to deliver cancer antigens to antigen presenting cells, release antigens into cytosol, and promote the maturation of these cells. We earlier achieved cytosolic delivery of antigens and induction of antigen-specific cytotoxic T lymphocytes using carboxylated polyglycidol or polysaccharide derivative-modified liposomes that can induce membrane fusion with endosomes in response to weakly acidic pH. Furthermore, pH-sensitivity and adjuvant properties of these polymers were enhanced strongly by introduction of hydrophobic carboxylated units to dextran. Against our expectations, these polymer-modified liposomes only slightly induce cancer immunity, probably because of the high hydrophobicity of spacer units. This study used a polysaccharide with charged groups (chondroitin sulfate) instead of dextran as a backbone to reduce hydrophobicity. Chondroitin sulfate derivative-modified liposomes showed almost equal pH-sensitivity to that of dextran derivative-modified liposomes and achieved selective delivery to dendritic cells, whereas dextran derivative-modified liposomes were highly taken up by both dendritic cells and fibroblasts. Chondroitin sulfate derivative-modified liposomes delivered model antigenic proteins into cytosol of dendritic cells and promoted cytokine production from the cells, leading to tumor regression on tumor-bearing mice after subcutaneous administration. Results demonstrate that charged groups having polysaccharide as a backbone can be used in an effective strategy to balance strong hydrophobicity of spacer units with their utilization for immunity-inducing systems.

    DOI: 10.1021/acs.bioconjchem.9b00221

    PubMed

    Repository URL: http://hdl.handle.net/10466/0002000050

  • Emerging paradigms in nanotechnology for imaging and treatment of cerebral ischemia. Reviewed International coauthorship

    Sathyasivam Kaviarasi, Eiji Yuba, Atsushi Harada, Uma Maheswari Krishnan

    Journal of Controlled Release   300   22 - 45   2019.04( ISSN:0168-3659

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    Cerebral ischemia is a deadly condition that arises due to blockage of the blood vessels in the brain leading to oxygen deficiency thereby arresting brain functions and resulting in death or permanent impairment. Though a myriad of factors has been proposed to cause cerebral ischemia, it has been generally regarded as an old age-associated malady. However, unhealthy diet, stressful lifestyle and deteriorating environment quality has dramatically reduced the age on onset as well as the number of victims in recent years. Hence, there exists a need for prompt and effective therapeutic strategies for immediate as well as long-term damage control and maintenance of the functions of the brain, as well as early and accurate diagnosis of the risk of stroke or extent of damage after stroke. The physiological barriers further complicate the development of therapeutic and diagnostic interventions for cerebral stroke. The advent of nanotechnology has initiated new vistas for more effective and superior therapeutic and imaging modalities for management of cerebral ischemia. This review provides an overview on the current knowledge on the mechanism and causative factors of cerebral ischemia, drawbacks of conventional therapy as well as molecular targets that are being explored for stroke therapy. The review also discusses in detail the advances made using nano-interventions for therapy and imaging of stroke-affected regions along with their pros and cons. Emergent multi-functional nanoparticles for stroke management have also been reviewed.

    DOI: 10.1016/j.jconrel.2019.02.031

    PubMed

  • Sonodynamic Therapeutic Effects of Sonosensitizers with Different Intracellular Distribution Delivered by Hollow Nanocapsules Exhibiting Cytosol Specific Release. Reviewed

    Ryoma Teranishi, Takayuki Matsuda, Eiji Yuba, Kenji Kono, Atsushi Harada

    Macromolecular bioscience   19 ( 4 )   e1800365   2019.04( ISSN:1616-5187

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    Sonodynamic therapy (SDT) is a novel promising noninvasive therapy involving utilization of low-intensity ultrasound and sonosensitizer, which can generate reactive oxygen species (ROS) by sonication. In SDT, a high therapeutic effect is achieved by intracellular delivery and accumulation at the target sites of sonosensitizer followed by oxidative damage of produced ROS by sonication. Here, pH- and redox-responsive hollow nanocapsules are prepared through the introduction of disulfide cross-linkages to self-assembled polymer vesicles formed from polyamidoamine dendron-poly(l-lysine) for the efficient delivery of sonosensitizer. As sonosensitizer, doxorubicin (DOX), an anticancer drug accumulating into cell nucleus, is selected. Also, the conjugate of DOX and triphenylphosphonium (TPP-DOX) is synthesized as sonosensitizer with mitochondrial targeting ability. DOX and TPP-DOX are delivered to nucleus and mitochondria by nanocapsules. Furthermore, DOX- or TPP-DOX-loaded nanocapsules exhibit in vitro sonodynamic therapeutic effect to HeLa cells with sonication, which might be through oxidative damage to nucleus and mitochondria.

    DOI: 10.1002/mabi.201800365

    PubMed

  • Synthesis, Characterization, and Biomedical Applications of an Alkylated Quercetin-Gadolinium Complex Reviewed International coauthorship

    Kayiarasi Sathyasivam, Devi K, S. Shalini, Vinoth Perumal, Sridharan Vellaisamy, Yuba Eiji, Harada Atsushi, Krishnan Uma Maheswari

    ACS BIOMATERIALS SCIENCE & ENGINEERING   5 ( 3 )   1215 - 1227   2019.03( ISSN:2373-9878

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    DOI: 10.1021/acsbiomaterials.8b01254

  • pH応答性多糖とリポソームを基盤とした免疫誘導システムの開発 Invited Reviewed

    弓場英司

    高分子論文集 雑誌 J-STAGE   75 ( 5 )   433 - 443   2018.09

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  • Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro Reviewed

    M. Tsuruta, S. Ueda, P.Y. Yew, I. Fukuda, S. Yoshimura, H. Kishi, H. Hamana, M. Hirayama, J. Yatsuda, A. Irie, S. Senju, E. Yuba, T. Kamba, M. Eto, H. Nakayama, Y. Nishimura

    OncoImmunology 雑誌 Taylor & Francis online   7   2018.01

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  • TiO2ナノ粒子内包ポリイオンコンプレックスミセルによる疎水性プロドラッグの可溶化と超音波照射効果 Reviewed

    山本 聡, 古川 和樹, 小野 雅文, 弓場 英司, 原田 敦史, 河野 健司

    高分子論文集 雑誌 J-STAGE   75   42 - 47   2018.01

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  • Bleomycin-loaded pH-sensitive polymer-lipid-incorporated liposomes for cancer chemotherapy Reviewed

    E. Yuba, T. Osaki, M. Ono, S. Park, A. Harada, M. Yamashita, K. Azuma, T. Tsuka, N. Ito, T. Imagawa, Y. Okamoto

    Polymers 雑誌 MDPI   10   2018.01

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  • Evaluation of pH-sensitive fusogenic polymer-modified liposomes co-loaded with antigen and α-galactosylceramide as an anti-tumor vaccine Reviewed

    S. Okazaki, T. Iwasaki, E.Yuba, S. Watarai

    Journal of Veterinary Medical Science 雑誌 J-STAGE   80   197 - 204   2017.12

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  • Liposome-based immunity-inducing systems for cancer immunotherapy Reviewed

    E. Yuba

    Molecular Immunology 雑誌 Elsevier B.V.   98   8 - 12   2017.11

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    Repository URL: http://hdl.handle.net/10466/16174

  • Hyaluronic acid-based pH-sensitive polymer-modified liposomes for cell-specific intracellular drug delivery systems Reviewed

    M. Miyazaki, E. Yuba, H. Hayashi, A. Harada, K. Kono

    Bioconjugate Chem. 雑誌 ACS publication   29   44 - 55   2017.11

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    Repository URL: http://hdl.handle.net/10466/16172

  • pH-responsive micelle-based cytoplasmic delivery system for induction of cellular immunity Reviewed

    E. Yuba, N. Sakaguchi, Y. Kanda, M. Miyazaki, K. Koiwai

    Vaccines 雑誌 MPDI   5 ( 4 )   41   2017.11

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  • Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system Reviewed

    N. Yamazaki, S. Yamakawa, T. Sugimoto, Y. Yoshizaki, R. Teranishi, T. Hayashi, A. Kotaka, C. Shinde, T. Kumei, Y. Sumida, T. Shimizu, Y. Ohashi, E. Yuba, A. Harada, K. Kono

    J. Liposome Res. 雑誌 Taylor & Francis online   28   275 - 284   2017.09

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    Repository URL: http://hdl.handle.net/10466/16173

  • In vitro sonodynamic therapeutic effect of polyion complex micelles incorporating titanium dioxide nanoparticles Reviewed

    S. Yamamoto, M. Ono, E. Yuba, A. Harada

    Nanomaterials 雑誌 MDPI   7   2017.09

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  • Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly A sequences for effective vaccination Reviewed

    S. Uchida, N. Yoshinaga, K. Yanagihara, E. Yuba, K. Kataoka, K. Itaka

    Biomaterials 雑誌 Elsevier B.V.   150   162 - 170   2017.09

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  • Development of pH-sensitive dextran derivatives with strong adjuvant function and their application to antigen delivery Reviewed

    E. Yuba, S. Uesugi, M. Miyazaki, Y. Kado, A. Harada, K. Kono

    Membranes 雑誌 MDPI   7   2017.08

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  • pH-sensitive polymer-modified liposome-based immunity-inducing system: effects of inclusion of cationic lipid and CpG-DNA Reviewed

    Y. Yoshizaki, E. Yuba, N. Sakaguchi, K. Koiwai, A. Harada, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   141   272 - 283   2017.07

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    Repository URL: http://hdl.handle.net/10466/15729

  • Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon-ion irradiation Reviewed

    D. Kokuryo, I. Aoki, E. Yuba, K. Kono, S. Aoshima, J. Kershaw, T. Saga

    Translational Research 雑誌 Elsevier B.V.   185   24 - 33   2017.07

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  • Potentiation of cancer immunity-inducing effect by pH-sensitive polysaccharide-modified liposomes with combination of TGF-β type I receptor inhibitor-embedded liposomes Reviewed

    E. Yuba, S. Uesugi, Y. Yoshizaki, A. Harada, K. Kono

    Med. Res. Arch. 雑誌 KEI Journals   5 ( 5 )   2017.05

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  • Effect of the side chain spacer structure on the pH-responsive properties of polycarboxylates Reviewed

    A. Harada, R. Teranishi, E. Yuba, K. Kono

    Journal of Biomaterials Science: Polymer Edition, 雑誌 Taylor & Francis online   28   1028 - 1035   2017.05

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  • Preparation of dual-stimuli-responsive liposomes using methacrylate-based copolymers with pH and temperature sensitivities for precisely controlled release Reviewed

    T.Sugimoto, N. Yamazaki, T. Hayashi, E. Yuba, A. Harada, A. Kotaka, C. Shinde, T. Kumei, Y. Sumida, M. Fukushima, Y. Munekata, K. Maruyama, K. Kono

    Colloids and Surfaces B: Biointerfaces 雑誌 Elsevier B.V.   155   449 - 458   2017.04

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    Repository URL: http://hdl.handle.net/10466/15730

  • Dual-stimuli responsive liposomes using pH- and temperature-sensitive polymers for controlled transdermal delivery Reviewed

    N. Yamazaki, T. Sugimoto, M. Fukushima, R. Teranishi, A. Kotaka, C. Shinde, T. Kumei, Y. Sumida, Y. Munekata, K. Maruyama, E. Yuba, A. Harada, K. Kono

    Polymer Chemistry 雑誌 RSC publishing   8   1507 - 1518   2017.02

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    Repository URL: http://hdl.handle.net/10466/15731

  • Doxorubicin delivery using pH and redox dual-responsive hollow nanocapsules with a cationic electrostatic barrier Reviewed

    R. Teranishi, R. Matsuki, E. Yuba, A. Harada, K. Kono

    Pharmaceutics 雑誌 MDPI   9 ( 1 )   2016.12

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  • Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity Reviewed

    E. Yuba, A. Yamaguchi, Y. Yoshizaki, A. Harada, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   120   32 - 45   2016.12

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    Repository URL: http://hdl.handle.net/10466/15728

  • Induction of antibody response in the oral cavity of dogs following intraocular (eye drop) immunization with Porphyromonas gingivalis cell lysate incorporated in pH-sensitive fusogenic polymer-modified liposomes Reviewed

    Y. Shimizu, T. Iwasaki, T. Tajima, E. Yuba, K. Kono, S. Watarai

    J. Vet. Med. Sci 雑誌 J-STAGE   79 ( 2 )   290 - 298   2016.12

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  • Improvement of peptide-based tumor immunotherapy using pH-sensitive fusogenic polymer-modified liposomes Reviewed

    Y. Yoshizaki, E. Yuba, T. Komatsu, K. Udaka, A. Harada, K. Kono

    Molecules 雑誌 MDPI   21 ( 10 )   2016.09

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  • A cyclized helix-loop-helix peptide as a molecular scaffold for the design of inhibitors of intracellular protein-protein interactions by epitope and arginine grafting Reviewed International coauthorship

    D. Fujiwara, H. Kitada, M. Oguri, T. Nishihara, M. Michigami, K. Shiraishi, E. Yuba, I. Nakase, H. Im, S. Cho, J. Y. Joung, S. Kodama, K. Kono, S. Ham, I. Fujii

    Angew. Chem. Int. Ed. 雑誌 WILEY   55 ( 36 )   10612 - 10615   2016.08

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  • Magnetically- and near infrared light-powered supramolecular nanotransporters for the remote control of enzymatic reactions Reviewed

    S. A. Chechetka, E. Yuba, K. Kono, M. Yudasaka, A. Bianco, E. Miyako

    Angew. Chem. Int. Ed. 雑誌 WILEY   55   6476 - 6481   2016.04

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  • Design of pH-sensitive polymer-modified liposomes for antigen delivery and their application in cancer immunotherapy Reviewed

    E. Yuba

    Polymer Journal 雑誌 Nature publishing group   48   761 - 771   2016.03

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    Repository URL: http://hdl.handle.net/10466/15732

  • An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs Reviewed

    M. Hirayama, Y. Tomita, A. Yuno, H. Tsukamoto, S. Senju, Y. Imamura, M. A. Sayem, A. Irie, Y. Yoshitake, D. Fukuma, M. Shinohara, A. Hamada, H. Jono, E. Yuba, K. Kono, K. Yoshida, T. Tsunoda, H. Nakayama, Y. Nishimura

    OncoImmunology 雑誌 Taylor & Francis online   5   2016.01

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  • Multifunctional liposomes having target specificity, temperature-triggered release, and near-infrared fluorescence imaging for tumor-specific chemotherapy Reviewed

    K. Kono, M. Takashima, E. Yuba, A. Harada, Y. Hiramatsu, H. Kitagawa, T. Otani, K. Maruyama, S. Aoshima

    J. Control. Release 雑誌 Elsevier B.V.   216   67 - 77   2015.10

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  • pH-Sensitive polymer-liposome-based antigen delivery systems potentiated with interferon-γ gene lipoplex for efficient cancer immunotherapy Reviewed

    E. Yuba, Y. Kanda, Y. Yoshizaki, R. Teranishi, A. Harada, K. Sugiura, T. Izawa, J. Yamate, N. Sakaguchi, K. Koiwai, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   67   214 - 224   2015.10

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    Repository URL: http://hdl.handle.net/10466/00017521

  • PAMAM dendron lipid assemblies that undergo structural transition in response to weakly acidic pH and their cytoplasmic delivery capability Reviewed

    T. Doura, M. Yamada, R. Teranishi, Y. Yamamoto, T. Sugimoto, E. Yuba, A. Harada, K. Kono

    Langmuir 雑誌 ACS publication   31 ( 18 )   5105 - 5114   2015.05

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  • Gene expression of ternary complexes through the compaction of nanofiber-polyplexes by mixing with Lipofectamine Reviewed

    R. Aono, K. Nomura, E. Yuba, A. Harada, K. Kono

    Biomaterials Science 雑誌 RSC publishing   3   764 - 770   2015.05

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  • Facile construction of well-defined fullerene-dendrimer supramolecular nanocomposites for bioapplications Reviewed

    X. Li, Y. Watanabe, E. Yuba, A. Harada, T. Haino, K. Kono

    Chem. Commun. 雑誌 RSC publishing   51   2851 - 2854   2015.01

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  • In vivo remote control of bioreactions in Caenorhabditis elegans by carbon nanotube-liposome supramolecular nanohybrids Reviewed

    E. Miyako, S. A. Chechetka, M. Doi, E. Yuba, K. Kono

    Angew. Chem. Int. Ed. 雑誌 WILEY   54   9903 - 9906   2015

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  • Identification of Glypican-3-Derived Long Peptides Activating both CD8+ and CD4+ T-cells; Prolonged Overall Survival in Cancer Patients with Th Cell Response Reviewed

    M. A. Sayem, Y. Tomita, A. Yuno, M. Hirayama, A. Irie, H. Tsukamoto, S. Senju, E. Yuba, T. Yoshikawa, K. Kono, T. Nakatsura, Y. Nishimura

    OncoImmunology 雑誌 Taylor & Francis online   5   2015

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  • Enhancement of anti-tumor immune responses by transfection of IFNγ gene into tumor using a novel type synthetic vector Reviewed

    D. P. H. Wijesekera, K. Sugiura, E. Yuba, K. Ueda, V. Wijewardana, R. Kanegi, T. Nishimura, T. Ushigusa, S. Hatoya, K. Kono, T. Inaba

    Veterinary Immunology and Immunopathology 雑誌 Elsevier B.V.   162   59 - 64   2014.09

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  • Evaluation of temperature-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified-modified liposomes and MRI Reviewed

    D. Kokuryo, S. Nakashima, F. Ozaki, E. Yuba, K. H. Chuang, S. Aoshima, Y. Ishizaka, T. Saga, K. Kono, I. Aoki

    Nanomedicine-Nanotechnology, Biology and Medicine 雑誌 Elsevier B.V.   11   229 - 238   2014.09

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  • Dually functionalized dendrimers by temperature-sensitive surface modification and gold nanoparticle loading for biomedical application Reviewed

    K. Kono, K. Takeda, X. Li, E. Yuba, A. Harada, T. Ozaki, S. Mori

    RSC Adv. 雑誌 RSC publishing   4   27811 - 27819   2014.06

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  • Synthesis of oligoethylene glycol-modified hyperbranched polyglycidols for dual sensitization of liposomes to pH and temperature Reviewed

    K. Kono, T. Kaiden, E. Yuba, Y. Sakanishi, A. Harada

    J. Taiwan Institute of Chemical Engineers 雑誌 Elsevier B.V.   45   3054 - 3061   2014.06

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  • PEGylated PAMAM dendrimer-doxorubicin conjugate-hybridized gold nanorod for combined photothermal-chemotherapy Reviewed

    X. Li, M. Takashima, E. Yuba, A. Harada, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   35   6576 - 6584   2014.05

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  • Potentiation of pH-Sensitive Polymer-Modified Liposomes with Cationic Lipid Inclusion as Antigen Delivery Carriers for Cancer Immunotherapy Reviewed

    Y. Yoshizaki, E. Yuba, N. Sakaguchi, K. Koiwai, A. Harada, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   35   8186 - 196   2014.05

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    Repository URL: http://hdl.handle.net/10466/00017520

  • Preparation of PEG-modified PAMAM dendrimers having gold nanorod core and their application to photothermal therapy Reviewed

    X. Li, K. Takeda, E. Yuba, A. Harada, K. Kono

    J. Mater. Chem. B 雑誌 RSC publishing   2   4167 - 4176   2014.04

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  • Nanofiber polyplex formation based on the morphology elongation by the intra-polyplex PEG crowding effect Reviewed

    R. Aono, E. Yuba, A. Harada, K. Kono

    ACS Macro Lett. 雑誌 ACS publication   3   333 - 336   2014.03

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  • Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy Reviewed

    E. Yuba, N. Tajima, Y. Yoshizaki, A. Harada, H. Hayashi, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   35   3091 - 3101   2014.01

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    Repository URL: http://hdl.handle.net/10466/00017519

  • Intracellular environment-responsive stabilization of polymer vesicles formed from head-tail type polycations composed of polyamidoamine dendron and poly (L-lysine) Reviewed

    A. Harada, R. Matsuki, S. Ichimura, E. Yuba, K. Kono

    Molecules 雑誌 MDPI   18   12168 - 12179   2013.09

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  • Application of pH-sensitive fusogenic polymer-modified liposomes for development of mucosal vaccines Reviewed

    S. Watarai, T. Iwase, T. Tajima, E. Yuba, K. Kono, Y. Sekiya

    Veterinary Immunology and Immunopathology 雑誌 Elsevier B.V.   158   62 - 72   2013.05

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  • The application of pH-sensitive polymer-lipids to antigen delivery for cancer immunotherapy Reviewed

    E. Yuba, Y. Kono, A. Harada, S. Yokoyama, M. Arai, K. Kubo, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   34   5711 - 5721   2013.04

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    Repository URL: http://hdl.handle.net/10466/00017518

  • A liposome-based antigen delivery system using pH-sensitive fusogenic polymers for cancer immunotherapy Reviewed

    E. Yuba, A. Harada, Y. Sakanishi, S. Watarai, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   34   3042 - 3052   2013.04

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    Repository URL: http://hdl.handle.net/10466/00017517

  • PAMAM dendrimers with oxyethylene unit-enriched surface as biocompatible temperature-sensitive dendrimers Reviewed

    X. Li, Y. Haba, K. Ochi, E. Yuba, A. Harada, K. Kono

    Bioconjugate Chem. 雑誌 ACS publication   24   282 - 290   2013.02

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  • Efficiency of pH-sensitive fusogenic polymer-modified liposomes as a vaccine carrier Reviewed

    S. Watarai, T. Iwase, T. Tajima, E. Yuba, K. Kono

    Scientific World J. 雑誌 Hindawi Publishing Corporation   2013   903234   2012.12

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  • Carbon nanotube-liposome supramolecular nanotrains for intelligent molecular-transport systems Reviewed

    E. Miyako, K. Kono, E. Yuba, C. Hosokawa, H. Nagai, Y. Hagihara

    Nature communications 雑誌 Nature publishing group   3   2012.11

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  • Titanium dioxide nanoparticles-entrapped polyion complex micelles generating singlet oxygen in the cells by ultrasound irradiation for sonodynamic therapy Reviewed

    A. Harada, M. Ono, E. Yuba, K. Kono

    Biomaterials Science 雑誌 RSC publishing   1   65 - 73   2012.09

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  • pH-sensitive fusogenic 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG)-conjugated liposome induces antigen-specific cellular and humoral immunity Reviewed

    T. Hebishima, E. Yuba, K. Kono, S. Takeshima, Y. Ito, Y. Aida

    Clinical and Vaccine Immunology 雑誌 Juornal ASM   19   1492 - 1498   2012.07

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  • Effect of unsaturated alkyl chains on transfection activity of poly(amidoamine)dendron-bearing lipids Reviewed

    E. Yuba, Y. Nakajima, K. Tsukamoto, S. Iwashita, C. Kojima, A. Harada, K. Kono

    J. Control. Release 雑誌 Elsevier B.V.   160   552 - 560   2012.04

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    Repository URL: http://hdl.handle.net/10466/0002000049

  • Polyamidoamine dendron-bearing lipids as a non-viral vector: influence of dendron generation Reviewed

    K. Kono, R. Ikeda, K. Tsukamoto, E. Yuba, C. Kojima, A. Harada

    Bioconjugate Chem. 雑誌 ACS publication   23   871 - 879   2012.02

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  • Assemblies of polyamidoamine dendron-bearing lipids with various generations: their morphologies and abilities of gene transfection Reviewed

    S. Iwashita, Y. Hiramatsu, T. Otani, C. Amano, M. Hirai, H. Minematsu, H. Kitagawa, K. Oie, E. Yuba, K. Kono, M. Miyamoto, K. Igarashi

    J. Biomaterials Applications 雑誌 SAGE Juornals   27   445 - 456   2012.01

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  • 高性能pH応答性リポソームを用いた抗原デリバリーとがん免疫治療への応用

    弓場 英司,原田 敦史,坂西 裕一,渡来 仁,河野 健司

    Progress in Drug Delivery System 雑誌   20   85 - 90   2011.12

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    Authorship:Lead author   Publishing type:Research paper (conference, symposium, etc.)   Kind of work:Joint Work   International / domestic magazine:Domestic journal  

  • Dual signal-responsive liposomes for temperature-controlled cytoplasmic delivery Reviewed

    T. Kaiden, E. Yuba, A. Harada, Y. Sakanishi, K. Kono

    Bioconjugate Chem. 雑誌 ACS publication   22 ( 10 )   1909 - 1915   2011.08

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

  • Thermosensitive molecular assemblies from PAMAM dendron-based lipids Reviewed

    K. Kono, E. Murakami, Y. Hiranaka, E. Yuba, C. Kojima, A. Harada, K. Sakurai

    Angew. Chem. Int. Ed. 雑誌 WILEY   50   6332 - 6336   2011.05

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

  • Hollow nanocapsules prepared through stabilization of polymer vesicles formed from head-tail type polycations by introducing cross-linkages Reviewed

    A. Harada, S. Ichimura, E. Yuba, K. Kono

    Soft Matter 雑誌 RSC publishing   7 ( 10 )   4629 - 4635   2011.04

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

  • Multifunctional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy Reviewed

    K. Kono, S. Nakashima, D. Kokuryo, I. Aoki, H. Shimomoto, S. Aoshima, K. Maruyama, E. Yuba, C. Kojima, A. Harada, Y. Ishizaka

    Biomaterials 雑誌 Elsevier B.V.   32 ( 5 )   1387 - 1395   2011.02

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

  • Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes Reviewed

    E. Yuba, A. Harada, Y. Sakanishi, K. Kono

    J. Control. Release 雑誌 Elsevier B.V.   149 ( 1 )   72 - 80   2011.01

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    Authorship:Lead author   Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

    Repository URL: http://hdl.handle.net/10466/12482

  • pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity Reviewed

    E. Yuba, C. Kojima, A. Harada, Tana, S. Watarai, K. Kono

    Biomaterials 雑誌 Elsevier B.V.   31 ( 5 )   943 - 951   2010.01

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    Repository URL: http://hdl.handle.net/10466/12481

  • Synthesis of a polyamidoamine dendron-bearing lipid having sugar moieties and its use for preparation of nonviral gene vectors Reviewed

    T. Takahashi, E. Yuba, C. Kojima, A. Harada, K. Kono

    Res. Chemical Intermediates 雑誌 Springer   35 ( 8-9 )   1005 - 1014   2009.11

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  • Modification of liposome surface with ph-responsive polyampholytes for the controlled-release of drugs Reviewed International coauthorship

    L. T. Ng, E. Yuba, K. Kono

    Res. Chemical Intermediates 雑誌 Springer   35 ( 8-9 )   1015 - 1025   2009.11

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  • Preparation and characterization of complexes of liposomes with gold nanoparticles Reviewed

    C. Kojima, Y. Hirano, E. Yuba, A. Harada, K. Kono

    Colloids and Surfaces B: Biointerfaces 雑誌 Elsevier B.V.   66 ( 2 )   246 - 252   2008.10

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  • Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes Reviewed

    E. Yuba, C. Kojima, N. Sakaguchi, A. Harada, K. Koiwai, K. Kono

    J. Control. Release 雑誌 Elsevier B.V.   130 ( 1 )   77 - 83   2008.08

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    Repository URL: http://hdl.handle.net/10466/12480

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Books and Other Publications

  • Nanotherapeutics in Cancer Vaccination and Challenges

    T. Sai Chaitanya, Sharvil Narendra Patil, Sayantani Ghosh, Jayanta K. Pal, Eiji Yuba, Rajesh Kumar Gupta( Role: Contributor ,  Cross-presentation-based nanovaccine for cancer immunotherapy)

    Academic Press  2022.03  ( ISBN:9780128236864

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    Total pages:464   Responsible for pages:349-396  

  • 刺激応答性高分子ハンドブック

    弓場英司( Role: Contributor)

    エヌ・ティー・エス  2018.12  ( ISBN:978-4-86043-535-6

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    Total pages:806   Responsible for pages:497-506  

  • Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications

    Eiji Yuba( Role: Contributor)

    Elsevier  2018.10  ( ISBN:9780081019962

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    Responsible for pages:305-319  

  • 粉体の表面処理・複合化技術集大成-基礎から応用まで-

    弓場英司( Role: Contributor)

    テクノシステム  2018.07  ( ISBN:978-4-924728-81-3

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    Total pages:726   Responsible for pages:423-431  

  • ドラッグデリバリーシステム-バイオ医薬品創成に向けた組織、細胞内、核内送達技術の開発-

    弓場英司( Role: Contributor)

    シーエムシー  2018.06  ( ISBN:978-4-7813-1333-7

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    Total pages:280   Responsible for pages:138-146  

  • DDS先端技術の製剤への応用開発

    弓場英司( Role: Contributor)

    技術情報協会  2017.06  ( ISBN:978-4-86104-663-6

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    Total pages:492   Responsible for pages:270-282  

  • DDS先端技術の製剤への応用開発

    弓場英司( Role: Contributor)

    技術情報協会  2017.06  ( ISBN:978-4-86104-663-6

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    Total pages:492   Responsible for pages:304-312  

  • DDSキャリア作製プロトコル集

    弓場英司, 河野健司( Role: Contributor)

    シーエムシー  2015.08  ( ISBN:978-4-7813-1077-0

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    Total pages:262   Responsible for pages:42-52  

  • DDSキャリア作製プロトコル集

    河野健司, 弓場英司( Role: Contributor)

    シーエムシー  2015.08  ( ISBN:978-4-7813-1077-0

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    Total pages:262   Responsible for pages:89-98  

  • Mucosal Delivery of Biopharmaceuticals

    E. Yuba, K. Kono( Role: Contributor)

    Springer  2014.01 

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    Total pages:601   Responsible for pages:197-220  

  • ドラッグデリバリーシステムの新展開II-核酸医薬・抗体医薬・ワクチン医療を支えるDDS技術-

    弓場英司, 河野健司( Role: Contributor)

    シーエムシー  2012.03 

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    Total pages:278   Responsible for pages:189-197  

  • 超分子サイエンス&テクノロジー

    弓場英司, 河野健司( Role: Contributor)

    エヌ・ティー・エス  2009.05  ( ISBN:978-4-86043-309-3

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    Total pages:1340   Responsible for pages:1180-1185  

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MISC

  • 機能性高分子を用いたリポソームを基盤とする免疫誘導システムの開発 Invited International journal

    弓場英司

    日本医学館 バイオマテリアル-生体材料-   41 ( 1 )   20 - 21   2023.01

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  • 機能性高分子を用いたリポソームを基盤とする免疫誘導システムの開発

    弓場 英司

    バイオマテリアル-生体材料-   41 ( 1 )   20 - 21   2023.01( ISSN:1347-7080

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    近年,患者本人の免疫を利用して治療効果を得る免疫療法が効果的ながん治療法として注目を集めている.筆者は,抗原を封入したリポソームに,pH応答性高分子や様々な機能性分子を組み込むことで,体内で細胞傷害性T細胞を中心とした細胞性免疫を強力に誘導するためのバイオマテリアル開発を行ってきた.本研究の成果は,効果的ながん免疫療法実現のための抗原キャリアや新たなワクチン開発への展開が期待される.(著者抄録)

  • 腫瘍免疫活性化のためのポリカルボン酸結合抗体の創製 International journal

    弓場 英司

    上原記念生命科学財団研究報告集   35   1 - 5   2021.12

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  • 【ワクチンのためのバイオマテリアル】脂質性ナノ粒子を用いたワクチン Invited International journal

    弓場 英司

    バイオマテリアル-生体材料-   39 ( 2 )   94 - 99   2021.04( ISSN:1347-7080 ( eISSN:2434-0359

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    脂質性ナノ粒子は、抗原特異的免疫を誘導するナノワクチン開発のための抗原運搬体として広く利用されてきた。本稿では、抗原運搬体の物理化学的パラメーターが免疫細胞との相互作用やリンパ節への移行、アジュバント作用、抗原提示経路に及ぼす影響について概説した後、リポソーム、ミセル、ヘキソソーム、キューボソーム、ウイルス/古細菌膜との融合型脂質性ナノ粒子等について、その特性と免疫誘導機能について紹介し、効果的なワクチン開発のためのマテリアル設計について明らかにすることを目指した。(著者抄録)

  • 【ワクチンのためのバイオマテリアル】脂質性ナノ粒子を用いたワクチン

    弓場 英司

    バイオマテリアル-生体材料-   39 ( 2 )   94 - 99   2021.04( ISSN:1347-7080

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    脂質性ナノ粒子は、抗原特異的免疫を誘導するナノワクチン開発のための抗原運搬体として広く利用されてきた。本稿では、抗原運搬体の物理化学的パラメーターが免疫細胞との相互作用やリンパ節への移行、アジュバント作用、抗原提示経路に及ぼす影響について概説した後、リポソーム、ミセル、ヘキソソーム、キューボソーム、ウイルス/古細菌膜との融合型脂質性ナノ粒子等について、その特性と免疫誘導機能について紹介し、効果的なワクチン開発のためのマテリアル設計について明らかにすることを目指した。(著者抄録)

  • pH応答性高分子とリポソームを基盤とした免疫誘導システムの開発 International journal

    弓場英司

    日本医学館 Drug Delivery System   35   426 - 433   2020.11

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  • Impression of a young researcher Invited International journal

    Eiji Yuba

    38   90 - 90   2020.04

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  • Design of pH‐sensitive polymer‐based immunity‐inducing systems Invited International journal

    Eiji Yuba

    Drug Delivery System   34 ( 3 )   163 - 172   2019.07( ISSN:0913-5006 ( eISSN:1881-2732

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    免疫療法の発展のために、免疫担当細胞に抗原を運搬すると同時に活性化し、抗原特異的な細胞性免疫を誘導できる抗原キャリアが求められている。筆者らは、弱酸性pHに応答して膜融合性を発現する機能性高分子を抗原封入リポソームに修飾することで、細胞性免疫を効果的に誘導できる抗原キャリアを開発した。pH応答性高分子修飾リポソームは樹状細胞に効果的に取り込まれ、エンドソームの弱酸性pHに応答して膜融合性となりサイトゾルに抗原を運搬することで、抗原特異的な細胞性免疫を誘導した。さらに、アジュバント分子の組み込みや、生理活性多糖を基盤としたpH応答性高分子の利用により、担がんマウスにおいて強力な抗腫瘍免疫の誘導に成功した。(著者抄録)

    J-GLOBAL

    Other URL: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01971&link_issn=&doc_id=20190725270002&doc_link_id=10.2745%2Fdds.34.163&url=https%3A%2F%2Fdoi.org%2F10.2745%2Fdds.34.163&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 【DDSを支える高分子材料の精密設計・成形・構造制御技術】pH応答性高分子を基盤とした免疫誘導システムの設計

    弓場 英司

    Drug Delivery System   34 ( 3 )   163 - 172   2019.07( ISSN:0913-5006

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    免疫療法の発展のために、免疫担当細胞に抗原を運搬すると同時に活性化し、抗原特異的な細胞性免疫を誘導できる抗原キャリアが求められている。筆者らは、弱酸性pHに応答して膜融合性を発現する機能性高分子を抗原封入リポソームに修飾することで、細胞性免疫を効果的に誘導できる抗原キャリアを開発した。pH応答性高分子修飾リポソームは樹状細胞に効果的に取り込まれ、エンドソームの弱酸性pHに応答して膜融合性となりサイトゾルに抗原を運搬することで、抗原特異的な細胞性免疫を誘導した。さらに、アジュバント分子の組み込みや、生理活性多糖を基盤としたpH応答性高分子の利用により、担がんマウスにおいて強力な抗腫瘍免疫の誘導に成功した。(著者抄録)

  • Coping Ability Training Invited International journal

    Eiji Yuba

    Koubunshi   68 ( 2 )   75 - 75   2019.02

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  • 機能性高分子の表面修飾による細胞特異的リポソームDDSの設計 Invited International journal

    弓場英司

    粉体工学会誌 雑誌 粉体工学会   55 ( 7 )   389 - 396   2018.07

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  • DDS応用を指向した刺激応答性リポソームの設計 Invited Reviewed International journal

    弓場 英司, 原田 敦史

    ファルマシア 雑誌 J-STAGE   54   11 - 15   2018.01

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  • 免疫治療のためのDDS最前線 Invited Reviewed International journal

    弓場英司、原田敦史、河野健司

    高分子学会 高分子   65   435 - 440   2016.08

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  • pH応答性高分子を基盤としたがん免疫治療用抗原デリバリーシステムの設計 Invited International journal

    弓場英司

    日本医学館 Drug Delivery System   30 ( 2 )   160 - 161   2015.03

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  • がん免疫治療用抗原デリバリーシステムとしてのpH応答性ポリマー修飾リポソーム Invited International journal

    弓場英司

    日本医学館 バイオマテリアル-生体材料-   32 ( 1 )   42 - 44   2014.01

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  • pH応答性ポリマー修飾リポソームを用いた抗原デリバリーとがん免疫治療への応用 Invited Reviewed International journal

    弓場英司

    日本組織適合性学会 Major Histocompatibility Complex   20   181 - 189   2013.11

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  • バイオ機能リポソームと免疫治療 Invited International journal

    弓場英司, 河野健司

    化学同人 化学   68   66 - 67   2013.08

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  • 高分子の表面修飾による機能性リポソームの設計 Invited International journal

    河野健司, 弓場英司,

    日本膜学会 膜   36   183 - 190   2011.07

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  • 細胞内で機能するリポソーム Invited International journal

    河野健司, 弓場英司

    エヌ・ティー・エス 未来材料   9 ( 3 )   2009.03

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Presentations

  • pH応答性両親媒性高分子による脂質シート・ベシクルの形態制御

    金子 奈央, 高橋 周太郎, 嶋田 直彦, 弓場 英司, 丸山 厚

    日本DDS学会学術集会プログラム予稿集  2023.07  日本DDS学会

  • 機能性高分子を用いたリポソームを基盤とする免疫誘導システムの開発 Invited Domestic conference

    弓場英司

    第44回日本バイオマテリアル学会大会  2022.11  日本バイオマテリアル学会

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  • 糖に結合してTurn-on型蛍光を示す機能性高分子の合成

    後藤 佑斗, 北山 雄己哉, 弓場 英司, 原田 敦史

    日本バイオマテリアル学会大会予稿集  2022.11  日本バイオマテリアル学会

  • 機能性高分子を用いたリポソームを基盤とする免疫誘導システムの開発

    弓場 英司

    日本バイオマテリアル学会大会予稿集  2022.11  日本バイオマテリアル学会

  • 樹状細胞の活性と機能を特異的に増強するアジュバントによる腫瘍免疫治療効果の検討

    渡邊 駿一, 弓場 英司, 赤澤 隆, 鳩谷 晋吾, 金城 綾二, 稲葉 俊夫, 杉浦 喜久弥

    日本獣医学会学術集会講演要旨集  2022.09  (公社)日本獣医学会

  • がん免疫誘導のための機能性リポソームの設計 Invited Domestic conference

    弓場英司

    第4回大阪公立大学アカデミア創薬シンポジウム  2022.06  大阪公立大学創薬科学研究所

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  • Rational Design of Dendritic Molecule-Gold Nanorod Hybrids for Biomedical Applications Invited International conference

    Eiji Yuba

    The SPIRITS Symposium -Materials and Methodology toward Unraveling Biological Systems-  2022.03 

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  • 多糖の生理活性を利用した免疫誘導システムの設計 Invited Domestic conference

    弓場英司

    セルロース学会関西支部第17回若手セミナー2021  2021.12  セルロース学会

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  • 腫瘍微小環境へのサイトカイン遺伝子導入操作は内臓腫瘍モデルにおいて治療効果を発揮する(Manipulation of tumor microenvironment by cytokinegene transfection elicits therapeutic effects in a visceral tumor model)

    Watanabe Shunichi, Yuba Eiji, Hatoya Shingo, Inaba Toshio, Sugiura Kikuya

    日本免疫学会総会・学術集会記録  2021.11  (NPO)日本免疫学会

  • Design of pH-sensitive materials towards control of immune responses Invited Domestic conference

    Eiji Yuba

    CEMS Topical Meeting Online  2021.09  理化学研究所

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    Presentation type:Oral presentation (invited, special)  

  • サイトカイン遺伝子の腫瘍細胞への導入による微小環境内免疫状態の改変がもたらす治療効果の検討

    渡邊 駿一, 高木 彩夏, 弓場 英司, 桑村 充, 井澤 武史, 鳩谷 晋吾, 金城 綾二, 稲葉 俊夫, 杉浦 喜久弥

    日本獣医学会学術集会講演要旨集  2021.09  (公社)日本獣医学会

  • Immunity-controlling systems using pH-sensitive polymer-based antigen nanocarriers and albumin-fused cytokine Invited International conference

    Eiji Yuba

    4th G’L’owing Polymer Symposium in KANTO (GPS-K 2021)  2021.07  高分子学会関東支部

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    Presentation type:Oral presentation (invited, special)  

  • pH応答性分岐βグルカン修飾リポソームによる樹状細胞の活性化と抗腫瘍免疫の誘導

    柳原 慎, 北山 雄己哉, 弓場 英司, 原田 敦史

    日本DDS学会学術集会プログラム予稿集  2021.06  日本DDS学会

  • 刺激応答性ナノキャリアとMRI-pH応答性リポソームを中心に- Invited Domestic conference

    弓場英司

    第5回 MRI アライアンス・シンポジウム2020  2020.11  国立研究開発法人量子科学技術研究開発機構・量子医学・医療部門放医研

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    Presentation type:Oral presentation (invited, special)  

  • pH応答性高分子とリポソームを基盤とした免疫誘導システムの開発 Invited

    弓場 英司

    第36回日本DDS学会学術集会  2020.08  日本DDS学会

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    Presentation type:Oral presentation (invited, special)  

  • 光温熱免疫療法のためのデンドリマー-金ナノロッドハイブリッドの作製

    城中 直人, 弓場 英司, 原田 敦史, 北山 雄己哉

    日本DDS学会学術集会プログラム予稿集  2020.08  日本DDS学会

  • pH応答性高分子とリポソームを基盤とした免疫誘導システムの開発

    弓場 英司

    日本DDS学会学術集会プログラム予稿集  2020.08  日本DDS学会

  • pH応答性多糖を被覆させたカチオニックリポソームによる抗腫瘍免疫誘導能評価

    加生 希, 北山 雄己哉, 弓場 英司, 原田 敦史

    日本DDS学会学術集会プログラム予稿集  2020.08  日本DDS学会

  • pH応答性多糖修飾リポソームの取り込みメカニズムの解明

    三木 楓美子, 北山 雄己哉, 弓場 英司, 原田 敦史

    日本DDS学会学術集会プログラム予稿集  2020.08  日本DDS学会

  • pH応答性カードラン被覆正電荷リポソームによる腫瘍内マクロファージの極性化

    加生 希, 弓場 英司, 原田 敦史

    日本薬学会年会要旨集  2020.03  (公社)日本薬学会

  • pH応答性βグルカン修飾リポソームによる抗原特異的免疫の誘導と抗腫瘍効果

    柳原 慎, 弓場 英司, 原田 敦史

    日本薬学会年会要旨集  2020.03  (公社)日本薬学会

  • Design of pH-sensitive polymer-based immunity-inducing systems Invited International conference

    E. Yuba

    Post A2 China-Japan Biopolymer Symposium  2019.11 

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    Presentation type:Poster presentation  

  • pH-Responsive polysaccharide-based cellular immunity-inducing systems Invited International conference

    E. Yuba

    13th International Symposium on Nanomedicine  2019.11 

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    Presentation type:Oral presentation (invited, special)  

  • 表層官能基が異なるTiO2ナノ粒子超音波増感剤のDDS材料としての機能評価

    鈴木 咲和, 弓場 英司, 原田 敦史

    日本バイオマテリアル学会大会予稿集  2019.11  日本バイオマテリアル学会

  • 多分岐PEGによるアスペクト比を制御されたポリプレックスの安定性評価

    吉川 啓太, 弓場 英司, 原田 敦史

    日本バイオマテリアル学会大会予稿集  2019.11  日本バイオマテリアル学会

  • 抗原タンパク質とポリカルボン酸誘導体により被覆されたTiO2ナノ粒子含有ポリイオンコンプレックスの作製

    北川 美咲, 弓場 英司, 原田 敦史

    日本バイオマテリアル学会大会予稿集  2019.11  日本バイオマテリアル学会

  • 温度応答性ポリプレックス形態変化に基づく遺伝子発現効率向上

    原田 敦史, 勝圓 由紀子, 弓場 英司

    日本バイオマテリアル学会大会予稿集  2019.11  日本バイオマテリアル学会

  • pH応答性カードラン被覆正電荷リポソームによるマクロファージ極性化の検討

    加生 希, 弓場 英司, 原田 敦史

    日本バイオマテリアル学会大会予稿集  2019.11  日本バイオマテリアル学会

  • pH-Responsive polysaccharide-based antigen carriers for cancer immunotherapy Invited International conference

    E. Yuba

    2019 JSPS-NRF Joint Symposium  2019.01  JSPS-NRF

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    Presentation type:Oral presentation (invited, special)  

  • ポリカルボン酸誘導体とリポソームを基盤とした免疫誘導システムの構築 Invited Domestic conference

    弓場英司

    九州地区高分子若手研究会・冬の講演会  2018.11 

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    Presentation type:Oral presentation (invited, special)  

  • 機能性高分子を用いた免疫反応の制御とがん免疫療法への展開 Invited Domestic conference

    弓場英司

    第35回医用高分子研究会講座  2018.11 

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    Presentation type:Oral presentation (invited, special)  

  • pH-Responsive polysaccharide-based immunity-inducing systems Invited International conference

    E. Yuba, A. Harada

    China-Japan Joint Symposium on Biomaterials 2018  2018.11 

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    Presentation type:Oral presentation (invited, special)  

  • pH-Responsive polymer/lipid-based antigen carriers for cancer immunotherapy Invited International conference

    E. Yuba

    14th IUPAC International Conference NMS-XIII  2018.10  IUPAC

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    Presentation type:Oral presentation (invited, special)  

  • Design of pH-responsive polymer/lipid-based intracellular delivery systems and their application to cancer immunotherapy Invited International conference

    Eiji Yuba

    18th Symposium for Gene・Design and Delivery  2018.07  遺伝子・デリバリー研究会

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    Presentation type:Oral presentation (invited, special)  

  • Development of immunity-activating interfaces by surface modification of pH-sensitive polymers onto lipid membranes and their application to cancer immunotherapy Invited International conference

    Eiji Yuba

    Korea-Japan Joint Symposium: Smart Interface by Functional Polymers Complexes  2018.04  韓国高分子学会

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    Presentation type:Oral presentation (invited, special)  

  • pH-Responsive polysaccharide-modified liposomes for intracellular drug delivery Invited International conference

    E. Yuba

    13th IUPAC International Conference NMS-XIII   2017.10  IUPAC

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    Presentation type:Oral presentation (invited, special)  

  • Design of functional dendrimer-gold nanorod hybrids for biomedical applications Invited International conference

    E. Yuba, K. Kono

    IUPAC 17th International Symposium on MacroMolecular Complexes  2017.08  IUPAC

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    Presentation type:Oral presentation (invited, special)  

  • Liposome engineering for efficient cancer immunotherapy Invited International conference

    E. Yuba, K. Kono

    12th IUPAC International Conference NMS-XII  2016.10  IUPAC

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    Presentation type:Oral presentation (invited, special)  

  • 機能性高分子の表面修飾による細胞特異的リポソームDDSの設計 Invited Domestic conference

    弓場英司

    粉体工学会第52回夏期シンポジウム  2016.08  粉体工学会

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    Presentation type:Oral presentation (invited, special)  

  • Design of functional polymer-modified liposomes for antigen delivery and their application to cancer immunotherapy. Invited Domestic conference

    E. Yuba

    第64回高分子学会年次大会  2015.05  高分子学会

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    Presentation type:Oral presentation (invited, special)  

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Industrial Property Rights

  • Anti-inflammatory cytokines and methods of use

    Jeffrey Hubbell, Eiji YUBA, Elyse WATKINS, Jun Ishihara, Ako ISHIHARA

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    property_type:Patent 

    Application no:PCT/US2021/071587 

    Patent/Registration no:特許WO2022067334A1 

  • 末端修飾ポリアミドアミンデンドロン脂質

    弓場 英司, 仲谷 祐哉

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    property_type:Patent 

    Application no:特願2020-083267 

    Announcement no:特開2021-178780 

    J-GLOBAL

  • pH応答性リポソーム

    弓場 英司, 深谷 佳樹

     More details

    property_type:Patent 

    Application no:特願2017-136235 

    Announcement no:特開2019-019059 

    Patent/Registration no:特許第6901127号 

    J-GLOBAL

  • 正電荷脂質と多糖誘導体を含む微粒子担体

    弓場英司、河野健司、門柚奈、小岩井一倫、坂口奈央樹

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    property_type:Patent 

    Application no:特願2016-214408 

    Announcement no:特開2018-070539 

  • pH応答性を有する脂質、およびリポソーム

    山▲崎▼ 奈穂子, 粂井 貴行, 河野 健司, 弓場 英司, 山川 智史, 清水 透, 大橋 幸浩

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    property_type:Patent 

    Application no:特願2016-088834 

    Announcement no:特開2017-197463 

    Patent/Registration no:特許第6792347号 

    J-GLOBAL

  • pH応答性リポソーム

    弓場英司、田島直樹、河野健司

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    property_type:Patent 

    Patent/Registration no:特許第5866724号  

  • ポリグリシドール誘導体、及びこれを含む複合薬物担体

    河野健司、改田知宏、弓場英司、坂西裕一

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    property_type:Patent 

    Patent/Registration no:特許第5526318号  

  • 治療薬剤の標的部位への集積及び放出を追跡可能な治療薬剤含有リポソームおよびその製造方法

    菊池達也、青木伊知男、小高謙一、河野健司、弓場英司

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    property_type:Patent 

    Patent/Registration no:特許第5429710号  

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Collaborative research (seeds) keywords

  • アジュバント開発

  • がんワクチン

  • 細胞内への遺伝子・タンパク質・生理活性分子・抗がん剤導入

Outline of collaborative research (seeds)

  • がんワクチン

  • 生理活性分子の細胞内導入システム

  • 機能性リポソーム

Grant-in-Aid for Scientific Research

  • 免疫誘導におけるマテリアル設計の本質解明を指向したリンパ節標的抗原キャリアの構築

    2022

  • 腫瘍微小環境の理解に基づく効果的な治療法の開発

    2022

  • 低酸素下で形成される動的な代謝酵素集合体METAbody制御仮説の構築

    2022

  • 低侵襲性の反応性ナノ・マンガン造影剤開発による「MRI病理組織変性解析法」の創成

    2022

  • mRNA工学を基盤とした中分子mRNA医薬の創製とその治療応用

    2022

  • 神経芽腫難治微小病変の可視化とセラノスティクスによる新規治療開発

    2022

  • mRNA工学を基盤とした中分子mRNA医薬の創製とその治療応用

    2022

  • 低侵襲性の反応性ナノ・マンガン造影剤開発による「MRI病理組織変性解析法」の創成

    2021

  • mRNA工学を基盤とした中分子mRNA医薬の創製とその治療応用

    2021

  • 神経芽腫難治微小病変の可視化とセラノスティクスによる新規治療開発

    2021

  • 免疫誘導におけるマテリアル設計の本質解明を指向したリンパ節標的抗原キャリアの構築

    2021

  • 腫瘍微小環境の理解に基づく効果的な治療法の開発

    2021

  • 低酸素下で形成される動的な代謝酵素集合体METAbody制御仮説の構築

    2021

  • アジュバント機能一体型mRNAと標的指向性送達キャリアを用いたがんワクチン治療

    2020

  • アジュバント機能一体型mRNAと標的指向性送達キャリアを用いたがんワクチン治療

    2019

  • 正電荷脂質・機能性多糖ハイブリッドによる腫瘍免疫抑制解除システムの創出

    2018

  • アジュバント機能一体型mRNAと標的指向性送達キャリアを用いたがんワクチン治療

    2018

  • 免疫誘導機能の統合による高活性抗原ナノキャリアの創製と免疫治療への展開

    2017

  • 正電荷脂質・機能性多糖ハイブリッドによる腫瘍免疫抑制解除システムの創出

    2017

  • 免疫誘導機能の統合による高活性抗原ナノキャリアの創製と免疫治療への展開

    2016

  • 免疫誘導機能の統合による高活性抗原ナノキャリアの創製と免疫治療への展開

    2015

  • 抗原とサイトカイン遺伝子の同時送達により免疫を強力活性化できるナノワクチンの創製

    2014

  • 抗原とサイトカイン遺伝子の同時送達により免疫を強力活性化できるナノワクチンの創製

    2013

  • 蛋白質・遺伝子の同時送達により免疫反応を精密制御できるナノワクチンキャリアの開発

    2012

  • 蛋白質・遺伝子の同時送達により免疫反応を精密制御できるナノワクチンキャリアの開発

    2011

  • 高活性な免疫誘導を実現する多機能集積型ナノワクチンシステムの構築

    2010

  • 高分子とリポソームの複合化による高活性な多機能型ナノワクチンシステムの構築

    2009

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Contract research

  • がん免疫療法のための次世代型多糖ナノワクチンの開発

    独立行政法人 日本学術振興会  令和4(2022)年度 二国間交流事業共同研究・セミナー  2022

  • がん免疫療法のための次世代型多糖ナノワクチンの開発

    独立行政法人日本学術振興会  令和4(2022)年度 二国間交流事業共同研究・セミナー  2021

  • がん免疫療法のための次世代型多糖ナノワクチンの開発

    独立行政法人日本学術振興会  令和4(2022)年度 二国間交流事業共同研究・セミナー  2021

  • 組み換え蛋白質による肝臓細胞へのダイレクトリプログラミング法開発

    国立研究開発法人日本医療研究開発機構  再生医療実現拠点ネットワークプログラム 技術開発個別課題  2020

  • リポソームを用いた人工転写因子デリバリーシステムの開発と肝臓でのMMP/8発現誘導

    国立研究開発法人国立国際医療研究センター  2017

  • pH応答性高分子-デンドロン脂質ハイブリッドによる 核酸医薬送達用in vivoナノキャリアの創出

    国立研究開発法人科学技術振興機構  マッチングプランナープログラム  2016

  • リポソームを用いた人工転写因子デリバリーシステムの開発と肝臓でのMMP/8発現誘導

    国立研究開発法人国立国際医療研究センター  2016

  • pH応答性高分子-デンドロン脂質ハイブリッドによる 核酸医薬送達用in vivoナノキャリアの創出

    国立研究開発法人科学技術振興機構  マッチングプランナープログラム  2015

  • 多分岐pH応答性ポリマー修飾リポソームによる高活性型がん免疫ワクチンの開発

    国立研究開発法人科学技術振興機構  研究成果最適展開支援事業 FS(探索タイプ)  2011

  • 新規なpH 応答性ポリマー修飾リポソームを用いた高活性免疫ワクチンの開発

    国立研究開発法人科学技術振興機構  研究成果最適展開支援事業 FS(探索タイプ)  2010

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Incentive donations / subsidies

  • リンパ節内の免疫細胞を狙い撃ちするアルブミン結合機能性デンドリマーの創製

    公益財団法人池谷科学技術振興財団  2021

  • Don’t eat me シグナル阻害抗体を結合した金ナノハイブリッドによる光誘導免疫活性化システムの構築

    公益財団法人持田記念医学薬学振興財団  2020

  • ナノプラスチックが生体内で引き起こす免疫応答評価のための基礎的検討

    公益財団法人日揮・実吉奨学会  2020

  • アジュバント機能を有するポリカルボン酸誘導体の合成と免疫誘導システムへの展開

    公益財団法人野口研究所  2019

  • マンノース残基導入pH応答性カードラン修飾リポソームを用いる免疫細胞特異的抗原キャリアの構築

    公益財団法人稲盛財団  2019

  • 腫瘍免疫活性化のためのポリカルボン酸結合抗体の創製

    公益財団法人上原記念生命科学財団  2019

  • pH応答性ヒアルロン酸誘導体修飾リポソームを用いる免疫細胞特異的DDSの構築

    公益財団法人花王芸術・科学財団  2017

  • 糖残基を導入したデンドロン脂質の合成とデンドロン脂質集合体を用いる免疫細胞特異的DDSの開発

    公益財団法人旭硝子財団  2017

  • エキソソームと膜融合ポリマーのハイブリッド化による高活性ナノワクチンキャリアの創製

    公益財団法人内藤記念科学振興財団  2013

  • がん免疫治療のための多機能集積型抗原デリバリーシステムの開発

    公益財団法人テルモ科学技術振興財団  2013

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Charge of on-campus class subject

  • 化学外国語演習

    2023   Weekly class   Undergraduate

  • 有機化学演習IIA

    2023   Weekly class   Undergraduate

  • 応用化学実験III

    2023   Weekly class   Undergraduate

  • 物質化学生命系特別演習

    2023   Intensive lecture   Graduate school

  • 物質化学生命系特別研究第1

    2023   Intensive lecture   Graduate school

  • 物質化学生命系特別演習第1

    2023   Intensive lecture   Graduate school

  • 有機化学演習IIA

    2022   Weekly class   Undergraduate

  • 化学外国語演習

    2022   Weekly class   Undergraduate

  • 応用化学実験I

    2022   Practical Training   Undergraduate

  • 初年次ゼミナール

    2022   Weekly class   Undergraduate

  • 生体高分子化学特論 (応用化学分野)

    2022   Weekly class   Graduate school

  • 応用化学実験III

    2022   Practical Training   Undergraduate

  • 応用化学実験II

    2022   Practical Training   Undergraduate

  • 応用化学実験IV

    2022   Practical Training   Undergraduate

  • 応用化学実験V

    2022   Practical Training   Undergraduate

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Social Activities

  • 内閣府 総合知ワークショップ@大阪公立大学

    Role(s): Host, Planner, Logistic support, Report author

    内閣府・大阪公立大学  総合知ワークショップ  大阪公立大学  2022.08

     More details

    SDGs:

    Audience: University students, Graduate students, Researchesrs, Scientific organization, Governmental agency

    Type:Seminar, workshop

    Number of participants:69(人)

Media Coverage

  • がん免疫を強く賦活するDDS Internet

    医薬経済社  医薬経済online  https://iyakukeizai.com/iyakukeizaiweb/detail/177226  2022.12

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  • 従来比1/10の抗原量でがん免疫を強力に活性化 大阪公立大がDDS材料開発 Newspaper, magazine

    科学新聞  科学新聞  https://sci-news.co.jp/topics/6895/  2022.11

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  • 大阪公立大、少量でがん免疫活性化、DDS材料開発 Newspaper, magazine

    化学工業日報  化学工業日報  https://chemicaldaily.com/archives/224982  2022.11

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  • 大阪公立大、少ない抗原で細胞性免疫を活性化させる多糖修飾リポソームを開発 Newspaper, magazine

    日経バイオテク  日経バイオテクOnline  https://bio.nikkeibp.co.jp/atcl/news/p1/22/11/04/10117/?n_cid=nbpbto_mled_am  2022.11

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  • がん免疫療法に新たなワクチン材料開発 少量で成長を抑制と大阪公立大が発表 Newspaper, magazine

    日刊ゲンダイ  日刊ゲンダイDIGITAL  https://www.nikkan-gendai.com/articles/view/life/313827  2022.11

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  • 少量でがん免疫を活性化 ワクチン材料開発―大阪公立大 Newspaper, magazine

    日刊薬業  日刊薬業  https://nk.jiho.jp/article/175656  2022.11

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  • 少量でがん免疫を活性化 ワクチン材料開発 大阪公立大 Newspaper, magazine

    時事通信社  時事メディカル  https://medical.jiji.com/news/54769  2022.11

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  • 少量でがん免疫を活性化 ワクチン材料開発 大阪公立大 Newspaper, magazine

    時事通信社  時事ドットコム  https://www.jiji.com/jc/article?k=2022110200146&g=soc  2022.11

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  • バイオマテリアル研究で効果的な免疫療法につなげる Internet

    稲盛財団  3S研究者探訪  2022.09

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  • 抗がん・造影剤入りナノ粒子、放医研が開発 重粒子線治療と併用可 Newspaper, magazine

    日刊工業新聞  https://www.nikkan.co.jp/articles/view/00426024  2017.04

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  • 重粒子線とナノ薬剤併用で腫瘍縮小 Newspaper, magazine

    化学工業日報  2017.04

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Academic Activities

International exchange activities

  • 二国間共同研究「がん免疫療法のための多機能性多糖被覆抗原ナノキャリアの開発」

    Field category :Research

    Country name :インド   2019.06 - 2023.09

Job title

  • Manager within the university

    Osaka Metropolitan University

    学長特別補佐  2022.04