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Vol. 14 (2022)

Bacterial Metabolism-Initiated Nanocatalytic Tumor Immunotherapy

https://doi.org/10.1007/s40820-022-00951-0
Wencheng Wu
The State Key Lab of High Performance Ceramics and Superfne Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Shanghai Nanocatalytic Medicine in Specifc Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai 200050, People’s Republic of China
Yinying Pu
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Education Institute, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China
Shuang Gao
Digestive Endoscopy Center, Shanghai Fourth People’s Hospital to Tongji University, Shanghai 200081, People’s Republic of China
Yucui Shen
Digestive Endoscopy Center, Shanghai Fourth People’s Hospital to Tongji University, Shanghai 200081, People’s Republic of China
Min Zhou
Digestive Endoscopy Center, Shanghai Fourth People’s Hospital to Tongji University, Shanghai 200081, People’s Republic of China
Heliang Yao
The State Key Lab of High Performance Ceramics and Superfne Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Shanghai Nanocatalytic Medicine in Specifc Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai 200050, People’s Republic of China
Jianlin Shi
The State Key Lab of High Performance Ceramics and Superfne Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Shanghai Nanocatalytic Medicine in Specifc Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai 200050, People’s Republic of China

Corresponding Author: Jianlin Shi

jlshi@mail.sic.ac.cn

Nano-Micro Letters, Vol. 14 (2022), Article Number: 220

Abstract

The low immunogenicity of tumors remains one of the major limitations of cancer immunotherapy. Herein, we report a bacterial metabolism-initiated and photothermal-enhanced nanocatalytic therapy strategy to completely eradicate primary tumor by triggering highly effective antitumor immune responses. Briefly, a microbiotic nanomedicine, designated as Cu2O@ΔSt, has been constructed by conjugating PEGylated Cu2O nanoparticles on the surface of an engineered Salmonella typhimurium strain (ΔSt). Owing to the natural hypoxia tropism of ΔSt, Cu2O@ΔSt could selectively colonize hypoxic solid tumors, thus minimizing the adverse effects of the bacteria on normal tissues. Upon bacterial metabolism within the tumor, Cu2O@ΔSt generates H2S gas and other acidic substances in the tumor microenvironment (TME), which will in situ trigger the sulfidation of Cu2O to form CuS facilitating tumor-specific photothermal therapy (PTT) under local NIR laser irradiation on the one hand. Meanwhile, the dissolved Cu+ ions from Cu2O into the acidified TME enables the nanocatalytic tumor therapy by catalyzing the Fenton-like reaction of decomposing endogenous H2O2 into cytotoxic hydroxyl radicals (·OH) on the other hand. Such a bacterial metabolism-triggered PTT-enhanced nanocatalytic treatment could effectively destroy tumor cells and induce a massive release of tumor antigens and damage-associated molecular patterns, thereby sensitizing tumors to checkpoint blockade (ICB) therapy. The combined nanocatalytic and ICB therapy results in the much-inhibited growth of distant and metastatic tumors, and more importantly, induces a powerful immunological memory effect after the primary tumor ablation.


Highlights:


1 Novel-designed microbiotic nanomedicine capable of targeting hypoxic tumor sites.
2 First paradigm of bacterial metabolism-initiated and photothermal therapy-enhanced nanocatalytic therapy for ablating tumors and inducing immunogenic cell death.
3 Strong antitumor immunity activation for abscopal tumors therapy.

Keywords

Bacterial metabolism In situ nanocatalytic therapy Immunotherapy
Wu, Wencheng, Yinying Pu, Shuang Gao, Yucui Shen, Min Zhou, Heliang Yao, and Jianlin Shi. 2022. “Bacterial Metabolism-Initiated Nanocatalytic Tumor Immunotherapy”. Nano-Micro Letters 14 (November):220. https://doi.org/10.1007/s40820-022-00951-0.
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