Dodecanol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA) nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro.
Dodecanol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA) nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro.
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DOI：
10.1016/j.colsurfb.2012.07.030
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发表时间：
2013-02
期刊：
影响因子：
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通讯作者：
Sujun Wang;Yanfeng Luo;Suyun Zeng;C. Luo;Li Yang;Zhiqing Liang;Yuanliang Wang
中科院分区：
文献类型：
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作者：
Sujun Wang;Yanfeng Luo;Suyun Zeng;C. Luo;Li Yang;Zhiqing Liang;Yuanliang Wang
以十二醇-聚(d，L-乳酸)、端氨基聚乙二醇和叶酸为原料，合成了叶酸偶联聚乳酸-b-聚乙二醇-叶酸(DOL-PLA-PEGFA)。采用溶剂挥发诱导界面自组装法制备了Dol-PLA-PEG-FA纳米粒子。考察了Dol-PLA-PEG-FA纳米粒的大小、临界胶束浓度(CMC)、细胞毒性和体外对癌细胞的选择能力。纳米粒子的尺寸在制备过程中表现出与聚合物浓度相关的现象，其多分散性指数(PDI)很小。测得其在水溶液中的临界胶束浓度为1.995×10−4g/L，远低于文献报道的嵌段共聚自组装胶束的临界胶束浓度。细胞毒性评价表明，所获得的NPs2对乳腺癌细胞和正常内皮细胞均无毒性，细胞对NPs的摄取表明，与正常成纤维细胞相比，NPs2对乳腺癌细胞具有更高的选择能力。提出了受体介导的内吞作用可能的途径机制。以上结果表明，Dol-PLA-PEG-FA聚合物及其纳米粒可作为一种安全的、具有较强肿瘤细胞靶向性的药物载体用于肿瘤化疗。
Folate-conjugated Dol-poly(d,l-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA), was synthesized from dodecanol-poly(d,l-lactic acid), amino-terminated poly(ethylene glycol) and folate.1H NMR proved the successful synthesis of Dol-PLA-PEG-FA. Nanoparticles (NPs) were further fabricated from Dol-PLA-PEG-FA by using solvent evaporation-induced interfacial self-assembly method. The size, critical micelle concentration (CMC), cytotoxicity and selecting capability to cancer cells in vitro were examined for Dol-PLA-PEG-FA NPs. The size of NPs showed polymer concentration-dependent phenomenon in the fabrication process, and its polydispersity index (PDI) was very narrow. The CMC was determined as 1.995×10−4g/L in aqueous solution, which is much lower than the reported CMC of block copolymer self-assemble micelles. The cytotoxicity evaluation revealed that the obtained NPs2 are non-toxic to either breast cancer cell or normal endothelial cells, and the cell uptake of NPs indicated that the NPs demonstrated much higher selecting capability to breast cancer cells compared to normal fibroblast cells. The possible receptor-mediated endocytosis pathway mechanism was proposed. Based on the above results, it could be concluded that Dol-PLA-PEG-FA polymer and its nanoparticles can be potentially used as a safe drug carrier with strong tumor cells targeting capability for tumor chemotherapy.