Abstract
The reactive oxygen species(ROS)generation efficiency is always limited by the extreme tumor mi-croenvironment(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 deliv-ery.The CDs were synthesized by using metformin and methylene blue(MB)via a hydrothermal method.The obtained metformin-MB CDs(MMCDs)exhibited a higher 1O2 quantum yield and NO generation efficiency under light emitting diode(LED)light irradiation.Noteworthily,the 1O2 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 signif-icantly 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.
基金项目
国家自然科学基金(52172033)
国家自然科学基金(22005280)
support of the Key Labora-tory of Structure and Functional Regulation of Hybrid Materials of the Ministry of Education,Anhui()
Key Laboratory of Environ-ment Friendly Polymer Materials of Anhui Province,China()
Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province,Anhui University,China()