Near-Infrared Laser-Responsive Nanoplatform for Photodynamic/Photothermal/Chemodynamic Combined Therapy

Abstract Surgical resection remains a conventional clinical strategy for melanoma treatment, yet it still suffers from considerable clinical bottlenecks, including difficult surgical operations and unintended damage to adjacent normal tissues. Herein, a multifunctional nanoplatform, CeO2-ICG@PDA (CeICP NPs), was constructed. In vitro experiments verified that CeICP NPs could act as both a chemodynamic therapy (CDT) inducer and an in situ oxygen-supplying unit under a hydrogen peroxide (H2O2) environment. Upon single 808 nm near-infrared laser irradiation (1.5 W/cm2, 10 min), the nanosystem was activated, with the local temperature rapidly rising to 64.6 °C, triggering combined photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT), as well as responsive release of singlet oxygen (1O2) and hydroxyl radicals (•OH). In vivo evaluations were performed on B16 tumor-bearing mice. Pharmacokinetic results demonstrated that CeICP NPs exhibited a blood half-life of 38.8 min, which was 15.5-fold longer than that of free indocyanine green (ICG). Dynamic fluorescence imaging and photothermal imaging (PTI) revealed that the fluorescence intensity at tumor sites in the CeICP group was 2.8 times higher than that of the free ICG group at 24 h post-intravenous injection, confirming the superior tumor-targeted accumulation capability of the nanosystem. Under NIR laser irradiation, the combined local thermal effect and abundant reactive oxygen species generated by CeICP-mediated PTT-PDT-CDT combined therapy achieved remarkable solid tumor suppression. This strategy is expected to break the limitations of traditional melanoma treatments and provide a theoretical reference for the development of intelligent nanomedicines.