Dr. Shima, Fumiaki
Institution
1. Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
2. Graduate School of Engineering, Osaka University, Suita, Japan.
Presentation day
Thursday 4:20 PM
TITLE
Manipulation of immune responses by the hydrophobicity of nanomaterial composed of amphiphilic poly(γ-glutamic acid)
Abstract
The new generation vaccines are safe but poorly immunogenic, and thus they require the
use of adjuvants, which enhance immune responses. However, conventional adjuvants fail to induce potent
immune responses, and their toxicity and side-effects hinder the clinical use. Moreover, manipulation of the
type (cellular/humoral immunity) and the induction level of immune responses has been eagerly required,
although no adjuvants have been achieved. In the development of nanoparticle-based vaccine adjuvants,
the hydrophobicity (grafting degrees of hydrophobic side chains or kind of hydrophobic side chains) is one
of the most important factors. It could control the interaction between the encapsulated antigens and/or
nanoparticles with immune cells. In this study, nanoparticles (NPs) composed of amphiphilic poly(γ-
glutamic acid) (γ-PGA) grafted with various grafting degrees of L-phenylalanine ethyl ester (Phe) were
prepared (γ-PGA-Phe) to evaluate the effect of hydrophobicity of vaccine carriers on cellular uptake,
activation of dendritic cells (DCs), and induction of antigen-specific immune responses. The uptake amount
of the encapsulated antigen by DCs was dependent on the hydrophobicity of γ-PGA-Phe NPs. Moreover,
the activation potential of DCs was able to control about 5 to 30-hold than the conventional vaccine, and
the cellular immunity was about 10 to 40-hold. Interestingly, the kind of hydrophobic side chains also
affected the interactions between DCs and NPs, and thus the type and the induction level of immune
responses were drastically changed. These results indicated that the hydrophobicity of NPs could control
the interactions with DCs, and thus achieve the manipulation of immune responses. Hydrophobically
modified γ-PGA NPs would provide safe and efficient nanoparticle-based vaccine adjuvants.
CV
2012-2015 Ph.D. students in Graduate School of Engineering, Osaka University, Jpn
2013-2015 JSPS Research Fellow (DC2)
2015 Ph.D. (Engineering), Graduate School of Engineering, Osaka University, Jpn
2015~ Specially Appointed Assistant Professor in Graduate School of Frontier Biosciences, Osaka University, Jpn
Literatures
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Takami Akagi, Fumiaki Shima, Mitsuru Akashi, Intracellular degradation and distribution of protein-encapsulated amphiphilic poly(amino acid) nanoparticles, Biomaterials, 32, 4959-4967 (2011).
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Fumiaki Shima, Koshi Kawakami, Takami Akagi, Eiko Mochizuki, Tetsuya Tsuda, Susumu Kuwabata, Mitsuru Akashi, Simple observation of the interaction between nanoparticles and cells by scanning electron microscopy employing ionic liquid, Bull. Chem. Soc. Jpn., 86, 153-158 (2013).
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Fumiaki Shima, Tomofumi Uto, Takami Akagi, Mitsuru Akashi, Synergistic stimulation of antigen presenting cells via TLR by combining CpG ODN and poly(γ-glutamic acid)-based nanoparticles as vaccine adjuvants, Bioconjugate Chem., 24, 926-933 (2013).
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Fumiaki Shima, Tomofumi Uto, Takami Akagi, Masanori Baba, Mitsuru Akashi, Size effect of amphiphilic poly(γ-glutamic acid) nanoparticles on cellular uptake and maturation of dendritic cells in vivo, Acta Biomater., 9, 8894-8901 (2013).
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Fumiaki Shima, Tomofumi Uto, Takami Akagi, Mitsuru Akashi, Manipulating the antigen-specific immune response by the hydrophobicity of amphiphilic poly(γ-glutamic acid) nanoparticles, Biomaterials, 34, 9709-9716 (2013).
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Fumiaki Shima, Bjoern Schulte, Helmut Keul, Martin Moeller, Mitsuru Akashi, Preparation of microparticles composed of amphiphilic poly(γ-glutamic acid) through hydrophobic interactions, Polym. J., 46, 184-188 (2014).
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Fumiaki Shima, Takami Akagi, Mitsuru Akashi, The role of hydrophobicity in the disruption of erythrocyte membrane by nanoparticles composed of hydrophobically modified poly(γ-glutamic acid), J. Biomater. Sci. Polym. Ed., 25, 203-210 (2014).
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Fumiaki Shima, Takami Akagi, Mitsuru Akashi, Synthesis and preparation of nanoparticles composed of amphiphilic poly(γ-glutamic acid) with different hydrophobic side chains and their potential of membrane disruptive activity, Colloid Polym. Sci., 292, 2663-2671 (2014).
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Fumiaki Shima, Takami Akagi, Mitsuru Akashi, The hydrophobic effect of nanoparticles composed of amphiphilic poly(γ-glutamic acid) on the degradability of the encapsulated proteins, Biomater. Sci., 2, 1419-1425 (2014).
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Fumiaki Shima, Manami Shudo, Takami Akagi, Mitsuru Akashi, Preparation of siRNA carrier based on boronic acid-functionalized amphiphilic poly(γ-glutamic acid) nanoparticles, Chem. Lett., 24, 840-842 (2014).
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Fumiaki Shima, Takami Akagi, Mitsuru Akashi, Effect of hydrophobic side chains in the induction of immune responses by nanoparticle adjuvants consisting of amphiphilic poly(γ-glutamic acid), Bioconjugate Chem., 26, 890-898 (2015).
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Fumiaki Shima, Takami Akagi, Manami Shudo, Eiko Mochizuki, Tetsuya Tsuda, Susumu Kuwabata, Mitsuru Akashi, Interaction between Living Cells and Polymeric Particles: Potential Application of Ionic Liquid for Evaluating the Cellular Uptake of Biodegradable Polymeric Particles Composed of Poly(amino acid), Polym. J., 47, 631-638 (2015).