甘草次酸—光敏剂纳米药物的构建及体外细胞活性研究OA

Objective:To address the inherent limitations of conventional chemotherapeutic agents,including low drug loading efficiency and a lack of light-controllable cytotoxicity,we developed a self-delivering,dual-functional nanodrug of CQ-GA-Fe NPs integrating chemodynamic therapy(CDT)and photodynamic therapy(PDT),assembled via Fe²⁺-mediated coordination using phosphorylated glycyrrhetinic acid(GA-P)as the ligand and phosphorylated carbazole-quinoline hexanol(CQ-P)as the photosensitizer,and the platform was preliminar-ily evaluated for its potential in the treatment of hepatocellular carcinoma.Methods:Key intermediates were sy-nthesized via nucleophilic substitution and condensation reactions.Subsequently,CQ-GA-Fe NPs were prepared through ion-coordination self-assembly and characterized using proton nuclear magnetic resonance spectroscopy(¹H-NMR)and Fourier-transform infrared spectroscopy(FT-IR).The pH-responsive drug release behavior was evaluated using dialysis method.The generation of hydroxyl radicals(·OH)and singlet oxygen(¹O ₂)was de-tected by methyl violet degradation and ABDA probe,respectively.Hemolysis assay was performed to evaluate its hemocompatibility.Cell counting kit-8(CCK-8)assay was used to detect its cytotoxicity against HepG2 and L02 cells and DCFH-DA fluorescent probe was adopted to measure the levels of intracellular reactive oxygen spe-cies(ROS).Results:The as-prepared CQ-GA-Fe NPs exhibited an average particle size of(202.0±1.6)nm,an average polydispersity index(PDI)of(0.130±0.029),and an average zeta potential of(-23.93±0.23)mV.In addi-tion,they demonstrated pH-responsive drug release behavior.Within 96 h,their average cumulative release rate at pH 6.8 reached(53.90%±3.14%),which was markedly higher than that at pH 7.4(37.98%±0.90%).Furthermore,CQ-GA-Fe NPs could generate ¹O₂ and·OH.In vitro experiments revealed that CQ-GA-Fe NPs exhibited negli-gible cytotoxicity toward normal L02 hepatocytes but exerted selective cytotoxicity against HepG2 cells through a strong synergistic effect of CDT and PDT(combination index CI＜0.16),with an IC ₅₀ value of 12.46 μg/mL.Conclusion:The constructed CQ-GA-Fe NPs demonstrate excellent biocompatibility and light-controlled selec-tive cytotoxicity against hepatocellular carcinoma cells.Through the strong synergistic effect of CDT and PDT,the constructed CQ-GA-Fe NPs induce intracellular ROS accumulation in the hepatocellular carcinoma cells and exert anti-tumor effects via oxidative stress,thus providing experimental evidence and theoretical references for multimodal synergistic therapy of hepatocellular carcinoma.