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

作者：Cai, Hao; Wu, Xiaoyan; Jiang, Lei; Yu, Feng; Yang, Yuxiang; Li, Yan; Zhang, Xian; Liu, Jian; Li, Zijian^*; Bi, Hong^*

来源：CHINESE CHEMICAL LETTERS, 2024, 35(4): 108946.

DOI：10.1016/j.cclet.2023.108946

• Carbon dots
• Nitric oxide
• Lysosome-targeting
• Photodynamic therapy
• Cancer

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.