Integrating Photothermal, Photodynamic, and Chemodynamic\nTherapies: The Innovative Design Based on Copper Sulfide Nanoparticles\nfor Enhanced Tumor Therapy

A multifunctional\nnanoplatform integrating multiple therapeutic\nfunctions may be an effective strategy to realize satisfactory therapeutic\nefficacy in the treatment of tumors. However, there is still a certain\nchallenge in integrating multiple therapeutic agents into a single\nformulation using a simple method due to variations in their properties.\nIn this work, multifunctional CuS-ICG@PDA-FA nanoparticles (CIPF NPs)\nwith excellent ability to produce reactive oxygen species and photothermal\nconversion performance are fabricated by a simple and gentle method.\nHollow mesoporous copper sulfide nanoparticles (HMCuS NPs) not only\nhave excellent loading and photothermal conversion performance but\nalso can cause a highly efficient Fenton-like reaction for chemodynamic\ntherapy (CDT). The loaded photosensitizer indocyanine green (ICG)\nimparts excellent photodynamic properties to the NPs, which in turn\nenhances the stability of ICG. The polydopamine (PDA) coating improves\nthe stability and biocompatibility of the NPs and creates the conditions\nfor surface modification of folic acid. The FA-coated NPs show precise\ntargeting of tumor cells. The results of the cellular uptake assay\ndemonstrate that CIPF NPs enter tumor cells through an endocytic pathway.\nLysosome colocalization and escape experiments prove that CIPF NPs\npossess good lysosomal escape ability under irradiation of NIR. Both <i>in vitro</i> and <i>in vivo</i> antitumor studies\nof CIPF NPs reveal excellent efficacy in photothermal/photodynamic/chemodynamic\ntherapy. The construction of high-performance CIPF NPs offers valuable\ninsights into the design of a multifunctional copper sulfide-based\nnanoplatform for combined cancer treatment and precise theranostics.