Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy

The reactive oxygen species (ROS) generation efficiency is always limited by the extreme tumor microenvironment (TME), leading to unsatisfactory antitumor effects in photodynamic therapy (PDT). As a promising gas therapy molecule, nitric oxide (NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots (CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue (MB) via a hydrothermal method. The obtained metformin-MB CDs (MMCDs) exhibited a higher 1 O2 quantum yield and NO generation efficiency under light emitting diode (LED) light irradiation. Noteworthily, the 1 O2 could further in situ oxidize NO into peroxynitrite anions (ONOO-), which own the higher cytotoxicity against cancer cells. Cell experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80% of HepG2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma HepG2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.