Integrating Photothermal, Photodynamic, and Chemodynamic Therapies: The Innovative Design Based on Copper Sulfide Nanoparticles for Enhanced Tumor Therapy

A multifunctional nanoplatform integrating multiple therapeutic functions may be an effective strategy to realize satisfactory therapeutic efficacy in the treatment of tumors. However, there is still a certain challenge in integrating multiple therapeutic agents into a single formulation using a simple method due to variations in their properties. In this work, multifunctional CuS-ICG@PDA-FA nanoparticles (CIPF NPs) with excellent ability to produce reactive oxygen species and photothermal conversion performance are fabricated by a simple and gentle method. Hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) not only have excellent loading and photothermal conversion performance but also can cause a highly efficient Fenton-like reaction for chemodynamic therapy (CDT). The loaded photosensitizer indocyanine green (ICG) imparts excellent photodynamic properties to the NPs, which in turn enhances the stability of ICG. The polydopamine (PDA) coating improves the stability and biocompatibility of the NPs and creates the conditions for surface modification of folic acid. The FA-coated NPs show precise targeting of tumor cells. The results of the cellular uptake assay demonstrate that CIPF NPs enter tumor cells through an endocytic pathway. Lysosome colocalization and escape experiments prove that CIPF NPs possess good lysosomal escape ability under irradiation of NIR. Both <i>in vitro</i> and <i>in vivo</i> antitumor studies of CIPF NPs reveal excellent efficacy in photothermal/photodynamic/chemodynamic therapy. The construction of high-performance CIPF NPs offers valuable insights into the design of a multifunctional copper sulfide-based nanoplatform for combined cancer treatment and precise theranostics.