Multifunctional superparamagnetic nanocarriers with folate-mediated and pH-responsive targeting properties for anticancer drug delivery.
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.
Key Laboratory of Functional Polymer Materials, Ministry of Education; and Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
Miao
M
Guo
Chailu
C
Que
Chenhong
C
Wang
Xiaozhou
X
Liu
Husheng
H
Yan
Keliang
K
Liu
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry*; D005434:Flow Cytometry; D005453:Fluorescence; D005492:Folic Acid / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D013997:Time Factors
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D011108:Polymers; C000499:ferric oxide; D004317:Doxorubicin; D005492:Folic Acid