载血卟啉PLGA微泡用于声动力治疗小鼠H22肝癌移植瘤

Effect of sonodynamic therapy on H22 tumor-bearing mice using hematoporphyrin-loaded PLGA ultrasound contrast agents

目的研究超声联合载血卟啉PLGA造影剂对小鼠H22肝癌皮下移植瘤的声动力治疗作用。方法自制载血卟啉高分子材料PLGA造影剂并检测其基本特性。选择30只荷H22肝癌皮下移植瘤小鼠,随机平均分为5组进行治疗,绘制治疗后15天内肿瘤体积生长曲线,比较其质量抑瘤率,并采用TUNEL和PCNA检测各组小鼠肿瘤细胞凋亡情况及增殖活性。结果自制的载血卟啉PLGA微泡造影剂平均粒径为602.3nm,分布均匀,包封率63.50%,载药量2.15%。治疗后,与其他各组比较,超声加载药微泡治疗组肿瘤生长曲线最平缓,质量抑瘤率及凋亡指数均显著高于其他4组(P<0.05),而增殖指数明显低于其他各组(P<0.05)。结论超声联合载血卟啉高分子纳米造影剂能够抑制小鼠H22肝癌移植瘤生长,促进其凋亡。

Objective To study the treatment effect on H22 tumor-bearing mice using ultrasound （US） combined with hematoporphyrin-loaded PLGA ultrasound contrast agents （HP-PLGA）. Methods Hematoporphyrin-loaded PLGA ultrasound contrast agents were prepared using the technique of double emulsion,and the properties of the contrast agents were detected. Then 30 H22 tumor-bearing mice were averagely divided into 5 groups for different treatment. The growth curve of H22 tumor was depicted within 15 days after treatment. The inhibition rate of tumor quality on the 15th day and the index about apoptosis and proliferation on tumor of each group were measured,respectively. Results Self-made hematoporphyrin-loaded PLGA ultrasound contrast agents had mean size of 602.3 nm with encapsulation efficiency of 63.50% and drug loading of 2.15%. After treatment,tumors of the E group （US＋HP-PLGA） grew most slowly compared with other groups. The inhibition rate of tumor quality and the apoptotic index in E group were significantly higher than those in other four groups （P〈0.05）,while the proliferation index in E group was significantly lower than that in other groups （P〈0.05）. Conclusion Ultrasound combined with hematoporphyrin-loaded PLGA ultrasound contrast agents could inhibit growth and promote the apoptosis of H22 tumor in mice,providing a novel strategy for sonodynamic therapy on the tumor.