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

Abstract

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.