Enhanced photodynamic therapy of TiO2/N-succinyl-chitosan composite for killing cancer cells

Abstract The aim of this study was to investigate the effect of TiO2/N-succinyl-chitosan composite (TiO2/ NSCS) photodynamic therapy (PDT), while considering the effects of various light sources on the activation of photosensitizer. The methyl thiazolyl tetrazolium assay was used to examine the cell survival rate of the cells. The results showed that glioma cell strain (U251) was the most sensitive cancer cell strain to TiO2/NSCS. When the concentration of TiO2/NSCS was between 0 and 800 μg·mL-1, there was no obvious cytotoxicity to normal liver cells (HL-7702) and U251 cells. During the PDT process, the photokilling effect of TiO2/NSCS on U251 cells under ultraviolet-A (UVA) light irradiation was stronger than that of pure TiO2, and its killing effects were positively correlated with concentration and irradiation time. In addition, both UVA and visible light could excite TiO2/ NSCS, which had significant killing effect on U251 cells. The results of acridine orange/ethidium bromide fluorescent double staining and Annexin V/propidium iodide double staining indicated that TiO2/NSCS under UVA and visible light irradiation could kill U251 cells by inducing apoptosis, and the apoptosis rate of TiO2/NSCS treatment groups was higher than that of TiO2 treatment groups. Therefore, TiO2/NSCS might be used as a potential photosensitizer in PDT.

摘要 本研究旨在探究二氧化钛/N-琥珀酰壳聚糖复合物（TiO₂/NSCS）介导的光动力疗法（PDT）的效果，并考察不同光源对光敏剂活化的影响。采用甲基噻唑基四唑（MTT）测定法检测细胞存活率。结果显示，胶质瘤细胞株（U251）是对TiO₂/NSCS最为敏感的癌细胞株。当TiO₂/NSCS浓度处于0~800 μg·mL⁻¹范围内时，对正常肝细胞（HL-7702）与U251细胞均无明显细胞毒性。在光动力治疗过程中，紫外-A（UVA）光照射下TiO₂/NSCS对U251细胞的光杀伤效应强于纯二氧化钛，且其杀伤活性与药物浓度及照射时长呈正相关。此外，UVA与可见光均可激发TiO₂/NSCS，对U251细胞具备显著杀伤作用。吖啶橙/溴化乙锭荧光双染色法及膜联蛋白V（Annexin V）/碘化丙啶双染色法结果表明，UVA及可见光照射下的TiO₂/NSCS可通过诱导细胞凋亡杀伤U251细胞，且TiO₂/NSCS处理组的细胞凋亡率高于纯二氧化钛处理组。因此，TiO₂/NSCS有望成为光动力疗法中潜在的光敏剂。