Surface-engineered CuFeS2/Camptothecin nanoassembly with enhanced chemodynamic therapy via GSH depletion for synergistic photo/chemotherapy of cancer

Abstract

Constructing the antitumor agents that are responsive to reactive oxygen species (ROS) have received considerable interest owing to their low drug resistance, high lethality of cytotoxic radicals such (•OH, •O2-, 1O2), and ease of combining with other therapeutic strategies. In this work, ROS-mediated therapies of quasi-spherical chalcogenide, CuFeS2 nanoparticles (NPs) were reported. Firstly, CuFeS2 NPs capped with oleylamine-capping agent were synthesized using the thermal decomposition technique, and surface modification was accomplished by micelles formation using an amphiphilic copolymer, pluronic 127 (PF127), to improve the water dispersibility of CuFeS2 NPs. The resulting material, CFS@PF nanoassembly, exhibited good dispersibility in an aqueous solution, which was attributed to the PF127 copolymer's hydrophilic property. Due to their strong absorption spectra in the near-infrared region (NIR), CFS@PF nanoassembly demonstrated remarkable photothermal conversion efficiency (PCE) of 63.3% upon NIR laser irradiation for photothermal therapy (PTT), which might induce hyperthermia in cancer treatment. Furthermore, CFS@PF nanoassembly could efficiently trigger not only singlet oxygen (1O2) under laser illumination for photodynamic therapy (PDT), but also cytotoxic hydroxyl radical (•OH) in the presence of peroxide solution (H2O2) for chemodynamic therapy (CDT) via Fenton reaction. Interestingly, the intracellular antioxidant, glutathione (GSH), could be effectively depleted via Cu–Fe-induced redox reaction, hence enhancing the efficacy of ROS-mediated therapeutics. In vitro experiments verified that CFS@PF NPs were more biocompatible with B16F1 and HeLa cells, but also exhibited substantial toxicity in the presence of laser and H2O2, resulting in 80% cell death through CDT/PDT/PTT synergistic effects. More crucially, CFS@PF micelles are employed in drug delivery for loading of Camptothecin (CPT), generating a CFS@PF/CPT nanoassembly for chemotherapy with a loading efficiency of 46.42%, and CPT release at various pH conditions was examined. The results of the cell experiments indicated that drug pairings boost tumor-killing performance by up to 90% due to the synergistic effect of CDT/PTT/chemotherapy. Overall, this study explored CFS@PF/CPT NPs, which might be potential anticancer agents for cancer therapy in the future of nanomedicine.