ISSN 1000-3304CN 11-1857/O6

高分子纳微球在工程疫苗中的新应用

岳华 马光辉

引用本文: 岳华, 马光辉. 高分子纳微球在工程疫苗中的新应用[J]. 高分子学报. doi: 10.11777/j.issn1000-3304.2019.19143 shu
Citation1:  Hua Yue and Guang-hui Ma. Applications of Polymeric Micro/Nanoparticles in Engineered Vaccines[J]. Acta Polymerica Sinica. doi: 10.11777/j.issn1000-3304.2019.19143 shu

高分子纳微球在工程疫苗中的新应用

    作者简介: 马光辉,女,1964年生. 中国科学院过程工程研究所生化工程国家重点实验室主任,基金委创新群体首席/杰青. 主要研究方向:均一生物微球和微囊的制备及其在生化工程中的应用,研究和开发用于生化分离、药物载体、免疫佐剂(疫苗递送系统)、细胞培养微载体、酶固定化载体等创新产品. 在Nat. Mater.、Nat. Commun.J. Am. Chem. Soc.、Adv. Mater. 等国际著名学术期刊上发表SCI论文385篇,3篇论文先后获得Elsevier出版集团高被引奖励. 出版中英文专著11部,中国发明专利授权81项,美国欧洲日本等国外专利授权11项,技术和产品在国内外500多家单位得到应用. 获得国家技术发明二等奖1项,北京市科学技术一等奖1项,第三世界科学院青年女科学家奖工程技术类第1名,亚洲生物技术协会(AFOB)-亚洲青年生物技术杰出贡献奖,中国化工学会侯德榜化工科技创新奖等. 目前担任J Encapsulation、IEC Research编委、中国化工学会生物化工专业委员会副主任委员、中国颗粒学会理事以及中国生物工程学会理事等职务;
    通讯作者: 马光辉, E-mail: ghma@ipe.ac.cn
摘要: 随着新发、突发重大传染病以及恶性肿瘤等疾病防控需求的增加,以经验开发为主的传统疫苗体系亟待更新. 高分子纳微球因其独特的理化优势,成为生物医药递送领域研究和关注的焦点. 但是如何对纳微球体系进行合理化设计和工程化整合是疫苗递送系统开发中遇到的重要挑战. 本团队20年来在高分子纳微球制备和应用方面进行了系统性研究,并提出纳微球为“底盘”(Chassis)和亚单位疫苗共组装成先进疫苗的策略,发现和创制了高分子纳微球新功能,阐明了其在细胞/黏膜免疫中的重要作用机理. 本专论结合国内外研究现状,围绕上述研究工作,介绍了工程化疫苗底盘按需设计的思路和参考机制,同时也探讨了其在生物医药领域的发展前景.

English

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  • Figure 1.  New strategy for advanced engineering vaccine by assembling the Chassis (micro/nanoparticles) and the components (antigens)

    Figure 2.  The process and instruments of membrane emulsification and its resultant particles (The fluorescent particle panel was reprinted with permission from Ref.[20], Copyright (2008) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

    Figure 3.  The effect of particle property on the cellular responses (Left panel was reprinted with permission from Ref.[15], Copyright (2010) Elsevier; Middle panel was reprinted with permission from Ref.[25], Copyright (2011) American Chemical Society; Right panel was reprinted with permission from Ref.[41], Copyright (2017) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

    Figure 4.  The scheme of three different particulate chassis with lysosomal escape merit:(a) Chitosan gel MP chassis (Reprinted with permission from Ref.[44]; Copyright (2014) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim), (b) PLA hollow chassis (Reprinted with permission from Ref.[45], Copyright (2015) American Chemical Society), (c) CaCO3 crystal NP chassis (Reprinted with permission from Ref.[46]; Copyright (2018) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

    Figure 5.  The unique properties of the 2D vaccine chassis for potent tumor vaccine: (a) 2D graphene oxide (GO) exhibiting a size-independent uptake event and selective internalization in phagocytes; (b) GO in micro size prefering to be fold in cells (left panel) and induces active cell recruitment (right panel) (a and b were reprinted with permission from Ref.[51], Copyright (2012) Elsevier); (c) High levels of cytokine secretion (upper left panel), membrane interaction (lower left panel), and the proposed signal activation pathways (right panel) upon the introduction of PEGylated GO (Reprinted with permission from Ref.[53]. Copyright (2017) Nature Publishing Group); (d) The scheme and corresponding evidences for the sandwiched graphene-based membrane superstructure (Reprinted with permission from Ref.[54], Copyright (2019) AAAS); (e) Efficient tumor inhibition after GO-OVA vaccination (Reprinted with permission from Ref.[55]; Copyright (2015) The Royal Society of Chemistry) (The online version is colorful.)

    Figure 6.  The mechanism and high efficiency of Pickering emulsion chassis in tumor vaccine: (a, b) Schematic illustration (a) and corresponding evidences (b) for the advantageous Pickering emulsion chassis. The merits includes ① high efficient construction, ② increased cell-chassis contact area and multiple recognition, and ③ charge reversal related lysosomal escape. (c) Potent adjuvanticity for H1N1 (upper) and MUC1 anti-tumor (lower) vaccination (Reprinted with permission from Ref.[53], Copyright (2017) Nature Publishing Group)

    Figure 7.  Solid emulsion chassis act as“immunoticket”and induces simultaneous systemic and gastrointestinal immune activations: (a) Schematic illustration on immunoticket strategy. (The immunoticket chassis cultivated the peripheral lymphocytes with gut homing receptors, which served as the “tickets”to hitchhike on the “express train”of CCL25 concentration gradient to the GALTs); (b) Schematic illustrations on the internal phase separation process to prepare immunoticket chassis; (c) Population of gut-infiltrated CTL (SIINFEKL-MHC I+ CCR9+ CD8+); (d) Anti-OVA IgA titers in the supernatant of intestinal trituration fluids (Reprinted with permission from Ref.[60], Copyright (2018) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

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  • 通讯作者:  马光辉, ghma@ipe.ac.cn
  • 收稿日期:  2019-08-02
  • 修稿日期:  2019-09-12
通讯作者: 陈斌, bchen63@163.com
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