Micro‐to‐Nano Oncolytic Microbial System Shifts from Tumor Killing to Tumor Draining Lymph Nodes Remolding for Enhanced Immunotherapy

Author:

Chen Zhichao1,Liu Yuhan1,Yu Yuxuan1,Yang Shihua2,Feng Jing1,Zhu Yinmei1,Huang Wanxu1,Qin Bin1,Guan Xinyao3,He Zhonggui1,Sun Mengchi4,Sun Jin1ORCID

Affiliation:

1. Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning 110016 China

2. Department of Surgical Oncology and General Surgery The First Hospital of China Medical University Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors China Medical University Ministry of Education Shenyang Liaoning 110001 China

3. Experimental Teaching Center Faculty of Functional Food and Wine Shenyang Pharmaceutical University Shenyang Liaoning 110016 China

4. School of Pharmacy Shenyang Pharmaceutical University Shenyang Liaoning 110016 China

Abstract

AbstractBecause 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., dendritic cells (DCs)) in TDLNs. Herein, this work develops the micro‐to‐nano oncolytic microbial therapeutics based on pyranose oxidase (P2O) overexpressed Escherichia coli (EcP) which are simultaneously encapsulated by PEGylated mannose and low‐concentrated photosensitizer nanoparticles (NPs). Following administration, P2O from this system generates toxic hydrogen peroxide for tumor regression and leads to the release of tumor antigens. The “microscale” EcP is triggered, following exposure to the laser irradiation, to secrete the “nanoscale” bacterial outer membrane vesicles (OMVs). The enhanced TDLNs delivery via OMVs significantly regulates the TDLNs immunomicroenvironment, promoting the maturation of DCs to potentiate tumor antigen‐specific T cells immune response. The micro‐to‐nano oncolytic microbe is leveraged to exert tumor killing and remold TDLNs for initiating potent activation of DCs, providing promising strategies to facilitate microbial cancer vaccination.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Natural Science Foundation of Liaoning Province

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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