Multifunctional superparamagnetic nanocarriers with folate-mediated and pH-responsive targeting properties for anticancer drug delivery

被引:119
作者
Guo, Miao [1 ,2 ]
Que, Chailu [1 ,2 ]
Wang, Chenhong [3 ]
Liu, Xiaozhou [1 ,2 ]
Yan, Husheng [1 ,2 ]
Liu, Keliang [3 ]
机构
[1] Nankai Univ, Minist Educ, Key Lab Funct Polymer Mat, Tianjin 300071, Peoples R China
[2] Nankai Univ, Inst Polymer Chem, Tianjin 300071, Peoples R China
[3] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China
基金
中国国家自然科学基金;
关键词
Drug delivery; Magnetism; Nanoparticle; Nanocarrier; pH-responsive; Folate-mediated targeting; POLYMERIC MICELLE; NANOPARTICLES; RECEPTOR; CANCER; ACRYLATE; RELEASE; PROTEIN; DESIGN;
D O I
10.1016/j.biomaterials.2010.09.077
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Multifunctional nanocarriers with multilayer core-shell architecture were prepared by coating superparamagnetic Fe3O4 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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:185 / 194
页数:10
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