A Tumor Microenvironment-Triggered and Photothermal-Enhanced Nanocatalysis Multimodal Therapy Platform for Precise Cancer Therapy

The tumor microenvironment (TME)-triggered therapeutic strategy not only provides effective and economical methods for cancer treatment but also minimizes the side effects on normal tissues. However, anticancer species generated by TME-triggered chemical reactions in situ within cancer cells are insufficient to inhibit tumor growth. This study reports the construction of a TME-triggered and photothermal (PT)-enhanced nanocatalysis platform that is based on cancer cell (MCF-7) membrane-camouflaged hollow porous Cu7S4 nanospheres (HPCu7S4@MCF-7) for efficient cancer therapy. HPCu7S4 exhibits strong absorption in the near-infrared region with a high PT conversion efficiency (∼30%). After coating with a cell membrane, HPCu7S4@MCF-7, which possesses a high ability to recognize and target cancer cells, can not only be used as a PT agent for PT therapy (PTT) but can also catalyze the generation of •OH and H2S under TME conditions to facilitate chemodynamic therapy (CDT) and gas therapy (GT), respectively. Moreover, NIR irradiation enhances the generation of more •OH and H2S to improve the therapeutic efficiency. Both in vitro and in vivo results demonstrate a high therapeutic efficiency of HPCu7S4@MCF-7-based PTT in combination with TME-triggered and PT-enhanced CDT and GT, which will open a new approach for constructing multimodal therapeutic strategies for potential use in the clinic.