Folate-conjugated amphiphilic star-shaped block copolymers as targeted nanocarriers.
Folate-conjugated amphiphilic star-shaped block copolymers as targeted nanocarriers.
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DOI：
10.1002/jbm.a.33071
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发表时间：
2011-06
期刊：
影响因子：
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通讯作者：
Jundong Zhu;Z. Zhou;Cuihong Yang;Deling Kong;Ying Wan;Zheng Wang
中科院分区：
文献类型：
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作者：
Jundong Zhu;Z. Zhou;Cuihong Yang;Deling Kong;Ying Wan;Zheng Wang
以L-丙交酯为原料，季戊四醇为引发剂，与甲氧基聚乙二醇(Mpeg)和叶酸-聚乙二醇(FA-peg)进行开环聚合，制备了叶酸(FA)-共聚星形聚合物作为靶向抗癌药物载体。得到的两亲性星形共聚物被塑造成载药胶束，所得胶束的平均直径约为146 nm。结果表明，模型药物(消炎痛)在部分胶束中的缓释时间可达40h左右，与线型聚(L-乳酸)-甲氧基-聚乙二醇单嵌段共聚物(PLAmGO)相比，星型季戊四醇-聚(L-乳酸)-嵌段[甲氧基聚乙二醇酯-聚乙二醇酯](PTL-PLAmEg/PEGFA)胶束的临界胶束浓度较低，稳定性明显提高。通过HeLa人宫颈癌细胞对PTL-PLA-mpeg/PEGFA和PTL-mpeg-mpeg的细胞内摄取实验，证实了PTL-pla-mpeg/peg-FA靶向肿瘤细胞的特异性。体外孵育2 h后，倒置荧光显微镜和流式细胞仪观察到PTL-PLA-mpeg/peg-FA在细胞内的摄取。这些结果表明，PTL-PLA-mpeg/peg-FA聚合物胶束可以作为一种潜在的载体，为FA受体阳性的癌细胞输送药物。
Folate (FA)-conjugated star-shaped copolymer was prepared as a targeted carrier for anticancer drug delivery by ring-opening polymerization of L-lactide using pentaerythritol (PTL) as an initiator, followed by conjugation with methoxy poly(ethylene glycol) (MPEG) and FA-poly(ethylene glycol) (FA-PEG). The resulting amphiphilic star-shaped copolymer was shaped into drug-loaded micelles, and the achieved micelles had an average size of around 146 nm in diameter. It was found that the sustained release time of model drug (indomethacin, IMC) from some selected micelles could reach around 40 h. In comparison with linear poly(L-lactic acid)-block-methoxy poly(ethylene glycol) copolymer (PLA-MPEG), the stability of the star-shaped pentaerythritol-co-poly(L-lactic acid)-block-[methoxy poly(ethylene glycol) and FA-poly(ethylene glycol)] (PTL-PLA-MPEG/PEG-FA) micelle was significantly improved because of the lower critical micelle concentration (CMC). The specificity of PTL-PLA-MPEG/PEG-FA targeting cancer cells was demonstrated by intracellular uptake of PTL-PLA-MPEG/PEG-FA and PTL-PLA-MPEG using HeLa human cervical cancer cells. After 2 h in vitro incubation, a significant intracellular uptake for PTL-PLA-MPEG/PEG-FA over PTL-PLA-MPEG was observed by using inverted fluorescence microscope and flow cytometry. These results suggested that PTL-PLA-MPEG/PEG-FA polymeric micelle could be a potentially useful carrier for delivering selected drugs to FA-receptor positive cancer cells.