Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
Adv Healthc Mater. 2019 Sep;8(17):e1900474. doi: 10.1002/adhm.201900474. Epub 2019 Jul 19.
A generic and effective tumor cells encapsulation strategy enabled by metal-organic coordination is developed to prepare a vaccine for personalized immunotherapy. Specifically, an epigallocatechin-3-gallate (EGCG)-Al(III) coordination layer is in situ formed onto individual living cells in aqueous phase and the process can be completed within an hour. 98% of proteins in the cells are entrapped within the microparticles, which are endowed with high antigens loading capacity. The microparticles enhance the uptake efficiency of antigens, protect antigens from degradation in vivo, and delay the retention time of antigens in the lymph nodes. Moreover, dendritic cells (DCs) activation is triggered by the microparticles, and simultaneously, the expression of costimulation marker on DCs and the production of Th1-related cytokines are significantly upregulated. Moreover, six kinds of tumor cells are utilized and successfully coated with the EGCG/Al(III) layer, suggesting the generalization of this strategy. More importantly, the microparticles exhibit a comparative antitumor effect with polyinosinic-polycytidylic acid (PolyI:C) in B16 pulmonary metastasis model. Overall, the encapsulation strategy enabled by metal-organic coordination can be potentially useful for personalized immunotherapy customized to individual patient's tumor cells.
一种通用且有效的基于金属有机配位的肿瘤细胞封装策略被开发出来，用于制备用于个性化免疫治疗的疫苗。具体而言，在水相中，将表没食子儿茶素没食子酸酯（EGCG）-Al（III）配位层原位形成到单个活细胞上，并且该过程可以在一小时内完成。细胞内 98%的蛋白质被包封在微颗粒内，该微颗粒具有高抗原负载能力。微颗粒提高了抗原的摄取效率，保护抗原在体内免受降解，并延长了抗原在淋巴结中的保留时间。此外，微颗粒触发树突状细胞（DC）的激活，同时，DC 上的共刺激标志物的表达和 Th1 相关细胞因子的产生显著上调。此外，利用六种肿瘤细胞成功地涂覆了 EGCG/Al（III）层，表明该策略具有通用性。更重要的是，在 B16 肺转移模型中，微颗粒与聚肌苷酸-聚胞苷酸（PolyI:C）表现出相当的抗肿瘤作用。总体而言，基于金属有机配位的封装策略可能对针对个体患者肿瘤细胞的个性化免疫治疗有用。
