摘要
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 higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could 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 Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.
基金
financially supported by the National Natural Science Foundation of China (Nos.52172033 and 22005280)
the support from the support of the Key Laboratory of Structure and Functional Regulation of Hybrid Materials of the Ministry of Education, Anhui University, China
the support from the Key Laboratory of Environment Friendly Polymer Materials of Anhui Province, China
Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Anhui University, China。