In vitro vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin-avidin interaction.
In vitro vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin-avidin interaction.
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DOI：
10.1016/j.ejps.2012.04.011
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发表时间：
2012-08
期刊：
影响因子：
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通讯作者：
X. Xiong;Liang Guo;Y. Gong;Zi-ling Li;Y. P. Li;Zhi Yong Liu;Ming Zhou
中科院分区：
文献类型：
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作者：
X. Xiong;Liang Guo;Y. Gong;Zi-ling Li;Y. P. Li;Zhi Yong Liu;Ming Zhou
本课题组成功合成了生物素化Pluronic F127/聚乳酸嵌段共聚物（B-F127-PLA）。本研究考察了紫杉醇B-F127-PLA纳米粒的体外释药行为及其对人卵巢癌细胞的靶向性。负载在B-F127-PLA纳米颗粒中的紫杉醇（pac）在前6小时内表现出初始爆发释放，然后缓慢释放。采用MTT法和荧光显微镜技术研究B-F127-PLA纳米粒对人卵巢癌细胞（OVCAR-3，SKOV-3）的体外靶向性。靶向基于三步生物素-抗生物素蛋白靶向方法，使用对CA-125抗原具有特异性的生物素化抗CA 125抗体，CA-125抗原在OVCAR-3细胞上高度表达，但在SKOV-3细胞上不表达。MTT结果显示，B-F127-PLA纳米粒中紫杉醇对OVCAR-3细胞的抗癌作用强于对SKOV-3细胞的抗癌作用，表明B-F127-PLA纳米粒更有效地递送至OVCAR-3细胞而不是SKOV-3细胞。FM技术进一步证实了B-F127-PLA纳米粒的靶向性。还使用三重标记方法研究了B-F127-PLA纳米粒的细胞内分布。观察到B-F127-PLA纳米颗粒主要位于OVCAR-3细胞的细胞质内。通过Balb/C裸鼠移植瘤OVCAR-3的肿瘤体积变化测量的三步法负载pac的B-F127-PLA纳米粒的体内抗肿瘤功效大于一步法。
Biotinylated Pluronic F127/poly(lactic acid) block copolymers (B-F127–PLA) were successfully synthesized previously by our group. In the present study, the release behaviors of paclitaxel-loaded B-F127–PLA nanoparticles and their targeting properties to human ovarian carcinoma cells were investigated. Paclitaxel (pac) loaded in B-F127–PLA nanoparticles shows an initial burst release in the first 6h and followed by a slow release. The in vitro targeting behaviors of B-F127–PLA nanoparticles against human ovarian cancer cells (OVCAR-3, SKOV-3) were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM) technique. Targeting was based on a three-step biotin–avidin targeting approach using biotinylated anti-CA125 antibody specific for the CA-125 antigen that is highly expressed on OVCAR-3 cells but not expressed on SKOV-3 cells. MTT results show that the anticancer effect of paclitaxel in B-F127–PLA nanoparticles over OVCAR-3 cells was stronger than that over SKOV-3 cells, indicating that B-F127–PLA nanoparticles were delivered more effectively to OVCAR-3 cells than to SKOV-3 cells. The targeting behaviors of B-F127–PLA nanoparticles were further confirmed by FM technique. The intracellular distribution of B-F127–PLA nanoparticles was also studied using a triple-labeling method. It was observed that B-F127–PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells. The in vivo antitumor efficacy of pac-loaded B-F127–PLA nanoparticles by three-step method as measured by change in tumor volume of OVCAR-3 implanted in Balb/C nude mice was greater than that by one-step method.