胃癌荷瘤小鼠应用四苯乙烯金属双环化合物靶向光敏剂进行光动力治疗的实验研究OA

Objective To verify the characteristics of tetraphenylethylene-based metallabicyclic compounds as targeted photosen-sitizers,including low dark toxicity and high reactive oxygen species(ROS)yield,and to provide a novel high-efficacy,low-tox-icity candidate targeted photosensitizer for photodynamic therapy(PDT)of gastric cancer.Methods A tetraphenylethylene-based metallabicyclic compound targeted photosensitizer was constructed using a multi-component coordination-driven self-assembly strategy.Human gastric cancer AGS and HGC-27 cells were used for in vitro experiments and divided into a light irradiation group(50 mW/cm2,10 min)and a dark group.The cytotoxicity was detected by CCK-8 assay,the cell killing performance was observed by live/dead cell staining,and intracellular ROS production was detected using fluorescence microscopy.A nude mouse model bearing gastric cancer xenografts was established to evaluate the in vivo antitumor efficacy and biosafety of the targeted photosensitizer.Results The tetraphenylethylene-based metallabicyclic compound targeted photosensitizer was success-fully constructed with a synthetic yield of 94％.Compared with the dark group,the light group exhibited significantly reduced IC50 values in AGS cells(7.58±0.40 μmol/L vs 37.05±3.67 μmol/L)and HGC-27 cells(5.70±0.34 μmol/L vs 35.16±4.05 μmol/L),with statistically significant differences(t=13.85,12.55,both P<0.05).A concentration of 6.5 μmol/L was selected for subsequent experiments.Live/dead cell staining revealed that cell death rates in the light group were significantly higher than those in the dark group,with values of 45.00％±0.40％vs 6.86％±0.84％in AGS cells and 85.98％±0.51％vs 8.63％±0.31％in HGC-27 cells(t=67.74,218.70,both P<0.05).Intracellular ROS mean fluorescence intensity was significantly higher in the light group than in the dark group,with values of 123.63±3.65 a.u.vs 48.89±3.22 a.u.in AGS cells and 154.54±12.31 a.u.vs 50.88±5.22 a.u.in HGC-27 cells(t=26.33,13.29,both P<0.05).In vivo,no significant difference in tumor volume was ob-served between the photosensitizer-alone group and the control group(t=0.56,P>0.05),while the tumor volume in the photo-sensitizer+light group was significantly reduced compared with that in the control group(t=3.04,P<0.05).There were no signif-icant changes in body weight of mice across all experimental groups during treatment(F=0.02,P>0.05).Conclusions The tetraphenylethylene-based metallabicyclic compound targeted photosensitizer has the characteristics of high synthetic yield,low dark toxicity,and high ROS production efficiency.It can achieve effective photodynamic killing in gastric cancer cells and has significant tumor inhibitory effect and favorable biosafety in vivo,making it a promising candidate targeted photosensitizer for PDT of gastric cancer.