期刊
BIOMATERIALS
卷 32, 期 1, 页码 185-194出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.09.077
关键词
Drug delivery; Magnetism; Nanoparticle; Nanocarrier; pH-responsive; Folate-mediated targeting
资金
- National Natural Science Foundation of China [20974052]
- National Key Technologies R & D Program for New Drugs of China [2009ZX09301-002]
- Natural Science Foundation of Tianjin Municipality [09JCZDJC22900]
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.
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