Reduction-degradable PEG-b-PAA-b-PEG triblock copolymer micelles incorporated with MTX for cancer chemotherapy.
Reduction-degradable PEG-b-PAA-b-PEG triblock copolymer micelles incorporated with MTX for cancer chemotherapy.
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DOI：
10.1016/j.colsurfb.2013.07.056
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发表时间：
2013-12
期刊：
影响因子：
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通讯作者：
Yong Sun;Yihang Huang;Shaoquan Bian;Jie Liang;Yujiang Fan;Xing‐dong Zhang
中科院分区：
文献类型：
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作者：
Yong Sun;Yihang Huang;Shaoquan Bian;Jie Liang;Yujiang Fan;Xing‐dong Zhang
以可还原降解的两亲性聚乙二醇-b-聚酰胺-b-聚乙二醇三嵌段共聚物(PEGb-PAA-b-PEG三嵌段共聚物)为原料，制备了可还原破碎的核壳型聚合物胶束，作为抗癌化疗药物甲氨蝶呤(MTX)的新型载体。通过Michael加成反应，在温和的条件下，一步合成了聚乙二醇-b-PAA-b-聚乙二醇共聚物。用该共聚物成功地制备了直径为65~123 nm的球形胶束。这些胶束可以有效地将抗癌药物MTX包裹在核心中，载药量约为13%。MTX的加入使胶束尺寸略有增大，但不影响胶束的形态。在没有DDT的情况下，药物在正常情况下几乎不能从胶束中释放，但在DTT的存在下，胶束核心结构被破坏时，药物在24小时内迅速释放到100%，为利用肿瘤组织中较高浓度的还原剂进行肿瘤靶向传递提供了潜在的工具。增殖抑制实验表明，MTX胶束对KB、HepG2和4T1肿瘤细胞，尤其是4T1肿瘤细胞具有明显的细胞毒作用。
Reduction-breakable core–shell type polymeric micelles from reduction-degradable amphiphilic polyethylene glycol-b–polyamide amine-b–polyethylene glycol triblock copolymers (PEG-b–PAA-b–PEG) were prepared as new drug carriers of methotrexate (MTX) for cancer chemotherapy. The PEG-b–PAA-b–PEG copolymers were synthesized in a simple one-step process under mild condition through Michael addition. Spherical micelles with diameters ranging from 65 to 123 nm were successfully fabricated from the copolymers. These micelles could effectively encapsulate the anti-cancer drug MTX in the core with drug loading content around 13%. The incorporation of MTX resulted in a little size increase but did not influence the morphology of micelles. The drug was hardly released from the micelles in normal condition without DDT as the reductant, but fast released up to 100% within 24 h when the structure of micelle core was broken in the presence of DTT, thus provided a potential tool for tumor targeting delivery of MTX using the higher concentration of reductant in tumor tissues. The proliferation inhibition experiments demonstrate that MTX-encapsulated micelles show significant cytotoxicity to KB, HepG2 and 4T1 tumor cells, especiallythe 4T1 cells.