中文摘要：研究对聚合物混合胶束（HMs）的理化性质进行了修饰，该胶束是由两种两亲性嵌段共聚物聚（乙二醇）磷酸乙醇胺（PEG-PE）和聚乙酰胺硬脂酸（PSA）通过疏水和静电作用形成的共轭聚合物。试验将黑色素瘤抗原肽Trp2和Toll样受体-9（TLR-9）促进剂CpG ODN整合到HMs中，其大小低于30nm。通过简单调节PEG-PE和PSA的比例可以修饰该聚合物的表面特性从而影响其体外动力学。研究结果表明，由PEG-PE和PSA按照1:1的比例形成的HMs聚合物能够靶向到淋巴腺近端从而通过DCs有效内化靶向物。同时，HMs介导的Trp2/CpG传递系统能够在很大程度上提高抗原特异性细胞毒性T细胞的数量，从而在肺转移性黑色素瘤模型中发挥强有效的抗肿瘤作用。
外文摘要： It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions. We successfully encapsulate melanoma antigen peptide Trp2 and Toll-like receptor-9 (TLR-9) agonist CpG ODN into HMs with a size of sub-30 nm. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by simply adjusting the molar ratio of PEG-PE and PSA. Our results demonstrated the optimized HMs with an equal mol of PEG PE and PSA can potently target proximal LNs where their cargos are efficiently internalized by DCs. Furthermore, HMs mediated Trp2/CpG delivery system greatly expands antigen specific cytotoxic T lymphocytes (CTLs) and offers a strong anti-tumor effect in a lung metastatic melanoma model.
外文关键词：Polymeric hybrid micelles； Lymph node； Targeting； Cytotoxic T lymphocytes； Melanoma； Vaccine
作者：Zeng, Q; Li, HM; Jiang, H; Yu, J; Wang, Y; Ke, H; Gong, T; Zhang, ZR; Sun, X Author Full Names: Zeng, Qin; Li, Hanmei; Jiang, Hao; Yu, Jiao; Wang, Ying; Ke, Huan; Gong, Tao; Zhang, Zhirong; Sun, Xun
作者单位：四川大学
期刊名称：BIOMATERIALS
期刊影响因子：18.96
出版年份：2017
出版刊次：4
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