Lysosome-targeted copper-modulated carbon dots with near-infrared fluorescence imaging and enhanced photodynamic therapy effects.

BACKGROUND: The excellent biocompatibility and tunable optical properties of carbon dots make them highly promising for applications in photodynamic therapy (PDT). However, effectively enhancing their photodynamic performance remains a significant challenge. This work employed methylene blue and metformin as precursors along with three trace metal elements ion (Fe, Zn and Cu) to synthesize carbon dots (CDs, FeCDs, ZnCDs and CuCDs) via a one-step hydrothermal method. RESULTS: The results demonstrate that metal ion doping effectively modulates the optical properties and photodynamic performance of carbon dots. Compared to CDs, the metal-doped carbon dots as synthesized exhibited red-shifted absorption and fluorescence emission wavelengths, alongside an increased fluorescence quantum yield and enhanced reactive oxygen species (ROS) generation. Among them, CuCDs displayed the most pronounced optical and photodynamic properties with fluorescence emission at 667 nm, and their ROS generation capacity was 9-fold higher than that of CDs. The CuCDs can specifically target the lysosomes of tumor cells, upon 660 nm laser irradiation, the resulting ROS disrupt the lysosomal membrane, thereby increasing lysosomal membrane permeability ultimately potentiating the photodynamic therapy effect and leading to a notable apoptosis rate of 87% in the tumor cells. SIGNIFICANCE AND NOVELTY: Thus, we constructed metal-ion-doped near-infrared carbon dots with organelle-targeting capability, which expected to enhance PDT efficacy by targeting lysosomes, promoting ROS generation, and disrupting their redox balance to exacerbate membrane damage. This work provides support for the construction of lysosome-targeted carbon dots through metal ion doping and shows their potential for application in near-infrared fluorescence imaging and PDT.