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Bacterial Metabolism-Initiated nanocatalytic Tumor Immunotherapy

Nano-Micro Letters 2022年第12期14卷 549-569页

作者： Wencheng Wu Yinying Pu Shuang Gao Yucui Shen Min Zhou Heliang Yao Jianlin Shi The State Key Lab of High Performance Ceramics and Superfine Microstructures Shanghai Institute of CeramicsChinese Academy of SciencesResearch Unit of Shanghai Nanocatalytic Medicine in Specific Therapy for Serious DiseaseChinese Academy of Medical Sciences(2021RU012)Shanghai 200050People’s Republic of China Department of Medical Ultrasound Shanghai Tenth People’s HospitalUltrasound Research and Education InstituteTongji University Cancer CenterTongji University School of MedicineShanghai 200072People’s Republic of China Digestive Endoscopy Center Shanghai Fourth People’s Hospital to Tongji UniversityShanghai 200081People’s Republic of China

The low immunogenicity of tumors remains one of the major limitations of cancer ***,we report a bacterial metabolisminitiated and photothermal-enhanced nanocatalytic therapy strategy to completely eradicate primary tumor by triggering highly effective antitumor immune ***,a microbiotic nanomedicine,designated as Cu_(2)O@ΔSt,has been constructed by conjugating PEGylated Cu_(2)O nanoparticles on the surface of an engineered Salmonella typhimurium strain(ΔSt).Owing to the natural hypoxia tropism ofΔSt,Cu_(2)O@ΔSt could selectively colonize hypoxic solid tumors,thus minimizing the adverse effects of the bacteria on normal *** bacterial metabolism within the tumor,Cu_(2)O@ΔSt generates H_(2)S gas and other acidic substances in the tumor microenvironment(TME),which will in situ trigger the sulfidation of Cu_(2)O to form CuS facilitating tumor-specific photothermal therapy(PTT)under local NIR laser irradiation on the one ***,the dissolved Cu+ions from Cu_(2)O into the acidified TME enables the nanocatalytic tumor therapy by catalyzing the Fenton-like reaction of decom-posing endogenous H_(2)O_(2) into cytotoxic hydroxyl radicals(·OH)on the other *** 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)*** 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.

关键词： Bacterial metabolism in situ nanocatalytic therapy Immunotherapy

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