Active Targeting Behaviors of Biotinylated Pluronic/Poly(Lactic Acid) Nanoparticles In Vitro through Three-Step Biotin–Avidin Interaction
Active Targeting Behaviors of Biotinylated Pluronic/Poly(Lactic Acid) Nanoparticles In Vitro through Three-Step Biotin–Avidin Interaction
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DOI：
10.1163/092050610x519444
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发表时间：
2011-01
期刊：
影响因子：
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通讯作者：
X. Xiong;Y. Gong;Zi-ling Li;Y. P. Li;Liang Guo
中科院分区：
文献类型：
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作者：
X. Xiong;Y. Gong;Zi-ling Li;Y. P. Li;Liang Guo
为了制备靶向药物载体，本课题组以前在Pluronic F87/聚乳酸和Pluronic P85/聚乳酸嵌段共聚物的末端连接了一个生物素基团，分别获得了B-F87-聚乳酸和B-P85-聚乳酸。本文通过生物素-亲和素三步相互作用，通过3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑溴化法和荧光显微镜(FM)研究了B-F87-聚乳酸和B-P85-聚乳酸纳米粒的体外活性靶向性。选择两种人卵巢癌细胞(OVCAR-3和SKOV-3)和紫杉醇进行细胞毒性实验。CA-125抗原在OVCAR-3细胞上高表达，而在SKOV-3细胞上不高表达。研究了紫杉醇在B-Pluronic-PLA纳米粒中的载药和释药行为。紫杉醇在B-F87-聚乳酸和B-P85-聚乳酸纳米粒中均表现出先快速释放后缓慢释放的特征。与SKOV-3细胞相比，载紫杉醇的B-Pluronic-PLA纳米粒由于表面生物素基团与OVCAR-3细胞表面的亲和素/生物素标记的单抗X306/CA-125抗原复合物的特异性相互作用，被更有效地输送到OVCAR-3细胞。利用FM进一步证实了B-F87-聚乳酸纳米粒的活性靶向性。
In order to prepare targeted drug carriers, previously a biotin group has been attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic P85/poly(lactic acid) block co-polymers to obtain B-F87–PLA and B-P85–PLA, respectively. In this paper, the active targeting properties of B-F87–PLA and B-P85–PLA nanoparticles in vitro were investigated through a three-step biotin–avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity tests. CA-125 antigen is over-expressed on OVCAR-3 cells but not on SKOV-3 cells. The loading and release behavior of paclitaxel loaded in B-Pluronic–PLA nanoparticles were also studied. Paclitaxel loaded in both B-F87–PLA and B-P85–PLA nanoparticles shows an initial rapid release followed by a slow release period. Compared with SKOV-3 cells, the cytotoxicity results implied that paclitaxel-loaded B-Pluronic–PLA nanoparticles were delivered more effectively to OVCAR-3 cells due to the specific interaction between the biotin groups on the surface of B-Pluronic–PLA nanoparticles and the avidin/biotinylated MAb X306/CA-125 antigen complexes on the surface of OVCAR-3 cells. The active targeting properties of B-F87–PLA nanoparticles were further confirmed by FM.