Micro-to-nano Oncolytic Microbial System Shifts from Tumor Killing to Tumor Draining Lymph Nodes Remolding for Enhanced Immunotherapy.

Because the tumor-draining lymph nodes (TDLNs) microenvironment is commonly immunosuppressive, oncolytic microbe-induced tumor antigens aren't sufficiently cross-primed tumor specific T cells through antigen-presenting cells (e.g., DCs) in TDLNs. Herein, we developed the micro-to-nano oncolytic microbial therapeutics based on pyranose oxidase (P2O)-overexpressed Escherichia coli (EcP) which were simultaneously encapsulated by PEGylated mannose and low-concentrated photosensitizer nanoparticles. Following administration, P2O from this system generated toxic hydrogen peroxide for tumor regression and led to the release of tumor antigens. The "microscale" EcP was triggered, following exposure to the laser irradiation, to secret the "nanoscale" bacterial outer membrane vesicles (OMVs). The enhanced TDLNs delivery via OMVs significantly regulated the TDLNs immuno-microenvironment, promoting the maturation of DCs to potentiate tumor antigen-specific T cells immune response. The micro-to-nano oncolytic microbe was leveraged to exert tumor killing and remold TDLNs for initiating potent activation of DCs, providing promising strategies to facilitate microbial cancer vaccination. This article is protected by copyright. All rights reserved.