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

TLDR

The authors propose coating drug‑loaded polymeric micelles with bacterial outer membrane vesicles to create a nanomedicine that enhances cancer immunotherapy and prevents metastasis. OMVs trigger host immune activation while the micelle‑encapsulated drug delivers chemotherapeutic and immunomodulatory effects that sensitize tumor cells to cytotoxic T lymphocytes and directly kill them. Systemic administration of this nanomedicine conferred protective immunity against melanoma, suppressed tumor growth, extended survival, inhibited lung metastasis, and demonstrates a versatile bacterial‑based platform for improving cancer immunotherapy.

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.