Bioengineering Bacterial Vesicle-Coated Polymeric Nanomedicine for Enhanced Cancer Immunotherapy and Metastasis Prevention

被引:260
作者
Chen, Qi [1 ]
Bai, Hongzhen [1 ]
Wu, Wangteng [1 ]
Huang, Guojun [1 ]
Li, Yang [1 ]
Wu, Min [1 ]
Tang, Guping [1 ]
Ping, Yuan [2 ]
机构
[1] Zhejiang Univ, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310028, Peoples R China
[2] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310013, Peoples R China
基金
中国国家自然科学基金;
关键词
Cancer therapy; biomimetic membrane coating; drug delivery; bacterial outer membrane vesicle; Salmonella; fluorouracil; IMMUNE-RESPONSES; SALMONELLA; 5-FLUOROURACIL; TYPHIMURIUM; CHECKPOINT; PROTECTION; VACCINES; THERAPY; CELLS;
D O I
10.1021/acs.nanolett.9b02182
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We herein propose a bioengineering approach where bacterial outer membrane vesicles (OMVs) were coated on drug-loaded polymeric micelles to generate an innovative nanomedicine for effective cancer immunotherapy and metastasis prevention. Whereas OMVs could activate the host immune response for cancer immunotherapy, the loaded drug within polymeric micelles would exert both chemotherapeutic and immunomodulatory roles to sensitize cancer cells to cytotoxic T lymphocytes (CTLs) and to kill cancer cells directly. We demonstrated that the systemic injection of such a bioinspired immunotherapeutic agent would not only provide effective protective immunity against melanoma occurrence but also significantly inhibited tumor growth in vivo and extended the survival rate of melanoma mice. Importantly, the nanomedicine could also effectively inhibit tumor metastasis to the lung. The bioinspired immunomodulatory nanomedicine we have developed repurposes the bacterial-based formulation for cancer immunotherapy, which also defines a useful bioengineering strategy to the improve current cancer immunotherapeutic agents and delivery systems.
引用
收藏
页码:11 / 21
页数:11
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