Reactive oxygen species augmented polydopamine-chlorin e6 nanosystem for enhanced chemo/photothermal/photodynamic therapy: A synergistic trimodal combination approach in vitro & in vivo

Amalgamation of near-infrared laser phototherapies with chemotherapy in multi-modal synergistic therapy holds great promise for future precision cancer nanomedicine due to its minimal invasiveness, reduced adverse reactions, and high anticancer efficacy. Herein, CuO nanoparticles were functionalized with photosensitizer molecule, chlorin e6 (Ce6) and coated with polydopamine (PDA) to achieve a drug delivery system (CuO@Ce6-PDA) with photothermal/photodynamic therapy (PTT/PDT). Subsequently, chemical drug PTX was loaded for chemotherapy, and folic acid (FA) serving as cancer-targeting exterior material. Prepared FA@CuO@Ce6-PDA/PTX nanoparticles were nano-sized with favorable biocompatibility, colloidal stability, optimal surface charge, effective PTX loading, and controllable PTX release. In vitro studies on 4T1 cells showed that FA@CuO@Ce6-PDA/PTX had noteworthy synergistic therapeutic antitumour effects featuring chemo/PTT/PDT with IC₅₀ of 50 μg/mL lower than that FA@CuO@Ce6-PDA/PTX without NIR laser irradiation (225 μg/mL). Additionally, FA@CuO@Ce6-PDA/PTX produced intracellular high reactive oxygen species (ROS) in presence of 660 nm laser, altering mitochondrial membrane potential and promoting tumour cell death. In vivo results indicate nanoplatform could accumulate in tumour spots enabling thermal imaging capabilities and exhibit synergistic therapeutic effect if irradiated with NIR laser (808 and 660 nm), evident from in vitro antitumour assay. Therefore, in vitro finding postulates FA@CuO@Ce6-PDA/PTX could be an intriguing nanoplatform for Chemo/PTT/PDT-based combination therapy.