载替拉扎明纳米凝胶增强肝癌介入栓塞治疗效果

Tirapazamine-loaded Nanogel Enhances the Therapeutic Effect of Interventional Embolization for Hepatocellular Carcinoma

目的制备载替拉扎明纳米凝胶用于VX2兔肝癌模型介入栓塞治疗,观察缺氧肿瘤细胞杀伤效果及总体疗效。方法培养HepG2人肝癌细胞系,观察替拉扎明在常氧及缺氧条件下对肿瘤细胞的杀伤效果。构建VX2兔肝癌模型,制备载替拉扎明纳米凝胶用于后续介入栓塞治疗。荷瘤兔分为对照组、替拉扎明灌注组、纳米凝胶栓塞组、替拉扎明纳米凝胶栓塞组。通过影像及病理、免疫荧光方法检测肿瘤生长率、坏死率及缺氧蛋白表达情况,评价各组治疗效果。结果替拉扎明可有效杀伤缺氧状态肿瘤细胞,纳米凝胶经导管动脉栓塞可使肝癌肿瘤细胞弥漫性缺氧,靶向杀伤肿瘤细胞的替拉扎明经导管肝动脉灌注可以杀伤肿瘤细胞但效果有限,载替拉扎明纳米凝胶对肝癌及缺氧状态肿瘤细胞有良好的杀伤效果。结论替拉扎明纳米凝胶可以有效地把替拉扎明的缺氧肿瘤靶向杀伤优势与纳米凝胶的血管栓塞特性结合起来优势互补,显著提高肝癌的介入栓塞治疗效果。

Objective To prepare nanogel containing tirapazamine for interventional embolization of V X2 rabbit liver cancer model,and to observe the killing effect and overall curative effect of hypoxic tumor cells.Methods HepG2 human hepatoma cell line was cultured,and the killing effect of tirapazamine on tumor cells under normal oxygen and hypoxia conditions was ob-served.VX2 rabbit liver cancer model was established,and tirapazamine-loaded nanogel was prepared for subsequent interven-tional embolization.The rabbits were divided into control group,tirapazamine perfusion group,nanogel embolization group and tirapazamine-loaded nanogel embolization group.The therapeutic effect of each group was evaluated by detecting tumor growth rate,necrosis rate and hypoxia protein expression by imaging,pa thology and immunofluorescence method.Results Tira-pazamine effectively killed tumor cells in hypoxic state.Nanogel transca theter arterial embolization resulted in diffuse hypoxia of liver cancer cells.T irapazamine targeting at killing tumor cells could kill tumor cells by transcatheter hepatic arterial infusion,but the effect was limited.Tirapazamine-loaded nanogel had good killing effect on liver cancer and hypoxic tumor cells.Conclusion Tirapazamine-loaded nanogel can effectively combine the targeted killing advantages of tirapazamine in hypox-ia with the characteristics of vascular embolization of nanogel,and complement each other,significantly improving the interven-tional embolization effect on liver cancer.