利用载舒尼替尼的多聚体微泡实现超声介导的靶向药物运输:实验研究

Sunitinib loaded polymer microbubbles for ultrasound triggered drug delivery: An experimental study

目的探索载舒尼替尼的新型多聚体型微泡抑制人肾癌GRC-1细胞增殖及诱导凋亡的作用。方法体外培养人肾癌GRC-1细胞,将其分为空白对照组、舒尼替尼组、新型多聚体型微泡联合超声组(pMB+US组)、载舒尼替尼的新型多聚体型微泡不联合超声组(pMBS-US组)、载舒尼替尼的新型多聚体型微泡联合超声组(pMBS+US组)。舒尼替尼组、pMBS-US组、pMBS+US组分别以0.01、0.10、1.00μg/ml舒尼替尼给予处理,于不同时间以MTT法观察不同处理组细胞生存率,检测细胞凋亡,并用HE染色法及DAPI荧光染色法观察凋亡细胞形态学改变。结果 pMBS+US组较之其余各组对肿瘤细胞有更为明显的抑制增殖及诱导凋亡效应(P<0.01)。结论载舒尼替尼的新型多聚体型微泡在超声作用下能显著促进药物与肿瘤细胞的作用,为靶向持续药物运输提供了可能。

Objective To investigate the effect of proliferation inhibition and apoptosis induction of sunitinib loaded poly- mer microbubbles on renal carcinoma cell strain GRC-I. Methods GRC-1 cell strain was cultured in vitro, and was divided into 5 groups, i.e. blank control group, sunitinib group （Sunitinib group）, new polymer microbubbles with ultrasound group （pMB＋ US group）, sunitinib loaded polymer microbuhbles without ultrasound group （pMBS--US group） and sunitinib loaded polymer microbubbles with ultrasound group （pMBS＋ US group）. Sunitinib group, pMBS--US group, pMBS＋ US group were pretreated with various concentration drugs （0.01, 0.10, 1.00 μg/ml）. MTT method was used to observe the cell survival rates of different treatment groups by changing the drug concentration. HE staining and DAPI flu- orescent staining were employed to detect apoptosis. Results The tumoricidal activity and apoptosis induction of pMBS＋ US group was significantly greater than that in other groups （P〈0, 01）. Conclusion Sunitinib loaded polymer microbub- bles can enhance drug delivery to tumor cells when triggered with focused ultrasound, which have potential value to provide a targeted and sustained delivery of drug to tumors.