Key Laboratory of Functional Polymer Materials, Ministry of Education; and Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
Biomaterials. 2011 Jan;32(1):185-94. doi: 10.1016/j.biomaterials.2010.09.077. Epub 2010 Nov 9.
Multifunctional nanocarriers with multilayer core-shell architecture were prepared by coating superparamagnetic Fe(3)O(4) nanoparticle cores with a mixture of the triblock copolymer methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-n-butyl methacrylate)-b-poly(glycerol monomethacrylate) and the folate-conjugated block copolymer folate-poly(ethylene glycol)-b-poly(glycerol monomethacrylate). The model anticancer agent adriamycin (ADR), containing an amine group and a hydrophobic moiety, was loaded into the nanocarrier at pH 7.4 by ionic bonding and hydrophobic interactions. The release rate of the loaded drug molecules was slow at pH 7.4 (i.e. mimicking the blood environment) but increased significantly at acidic pH (i.e. mimicking endosome/lysosome conditions). Acid-triggered drug release resulted from the polycarboxylate protonation of poly(methacrylic acid), which broke the ionic bond between the carrier and ADR. Cellular uptake by folate receptor-overexpressing HeLa cells of the folate-conjugated ADR-loaded nanoparticles was higher than that of non-folated-conjugated nanoparticles. Thus, folate conjugation significantly increased nanoparticle cytotoxicity. These findings show the potential viability of a folate-targeting, pH-responsive nanocarrier for amine-containing anticancer drugs.
具有多层核壳结构的多功能纳米载体是通过将超顺磁性 Fe(3)O(4)纳米颗粒核与三嵌段共聚物甲氧基聚乙二醇-b-聚（甲基丙烯酸-co-正丁基甲基丙烯酸）-b-聚（甘油单甲基丙烯酸酯）和叶酸偶联嵌段共聚物叶酸-聚乙二醇-b-聚（甘油单甲基丙烯酸酯）的混合物进行涂层制备而成的。模型抗癌药物阿霉素（ADR）含有一个胺基和一个疏水部分，通过离子键和疏水相互作用在 pH 7.4 下装载到纳米载体中。在 pH 7.4 时（即模拟血液环境），负载药物分子的释放速率较慢，但在酸性 pH 时（即模拟内体/溶酶体条件）显著增加。多羧酸的聚（甲基丙烯酸）质子化导致聚羧酸酯的质子化，从而破坏了载体与 ADR 之间的离子键，从而导致酸触发的药物释放。叶酸受体过表达的 HeLa 细胞对叶酸偶联的载有 ADR 的纳米颗粒的摄取高于非叶酸偶联的纳米颗粒。因此，叶酸缀合显著增加了纳米颗粒的细胞毒性。这些发现表明，对于含有胺的抗癌药物，叶酸靶向 pH 响应性纳米载体具有潜在的可行性。
