H2S‐Responsive NIR‐II Fluorescent Nanozyme that Regulates Tumor Microenvironment for Activatable Synergistic CO Therapy/Catalytic Therapy/Immunotherapy

Author:

Yang Fangqi12,Cao Xiang13,Yang Tonglin13,Feng Weifang13,Tong Qiang12,Liu Ketong12,Wu Luyan12,Lin Huihui45,Fan Quli12ORCID

Affiliation:

1. State Key Laboratory of Organic Electronics and Information Displays and Jiangsu Key Laboratory for Biosensors Institute of Advanced Materials (IAM) Nanjing University of Posts and Telecommunications Nanjing 210023 China

2. School of Materials Science and Engineering Nanjing University of Posts and Telecommunications Nanjing 210023 China

3. School of Chemistry and Life Sciences Nanjing University of Posts and Telecommunications Nanjing 210023 China

4. Department of Chemistry National University of Singapore 3 Science Drive 3 Singapore 117543 Singapore

5. Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science Technology and Research (A*STAR) Singapore 627833 Singapore

Abstract

AbstractNanozyme catalytic therapy triggered by the tumor microenvironment (TME)‐responsive enzyme‐like catalytic activities is an emerging approach for tumor treatment. However, the poor catalytic efficiency of nanozymes in tumors and the toxic side effects on normal tissues limit their further development, primarily due to the limited uptake and penetration depth of nanozyme in tumor tissues. Here, a tumor‐targeting TME and electric field stimuli‐responsive nanozyme (AgPt@CaCO3‐FA) is developed, which is capable of catalyzing the generation of ROS to induce cell death and releasing carbon monoxide (CO) specifically in tumor tissues for on‐demand CO therapy and immunotherapy. Benefiting from the endogenous H2S activated NIR‐II fluorescence (FL) imaging guidance, AgPt@CaCO3‐FA can be delivered into the deeper site of tumor tissues resulted from the TME regulation via generated CO during the electrolysis process to improve the catalytic efficiency of nanozymes in tumors. Moreover, CO effectively relieve immunosuppression TME via reeducating tumor‐supportive M2‐like macrophages to tumoricidal M1‐like macrophages and induce mitochondrial dysfunction by reducing mitochondrial membrane potential, triggering tumor cells apoptosis. The enzyme‐like activities combined with CO therapy arouse distinct immunogenic cell death (ICD) effect. Therefore, AgPt@CaCO3‐FA permits synergistic CO gas, catalytic therapy and immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Natural Science Research of Jiangsu Higher Education Institutions of China

Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions

Publisher

Wiley

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