title: Poly(ethylene glycol) shell-sheddable magnetic nanomicelle as the carrier of doxorubicin with enhanced cellular uptake.
abstract: This research is aimed to develop a kind of poly(ethylene glycol) shell-sheddable magnetic nanomicelle as the carrier of doxorubicin (Dox) in order to enhance its cellular uptake ability, and achieve synchronous magnetic resonance imaging (MRI)-visible function. Firstly, the five-member rings in poly (L-succinimide) (PSI) were successively opened by the amino terminated disulfide-linked poly(ethylene glycol) monomethyl ether (mPEG-SS-NH2) and dopamine (DA) to produce the graft copolymer of mPEG-SS-NH-graft-PAsp-DA. And then, drug-loaded magnetic nanomicelles of mPEG-SS-NH-graft-PAsp-DA@Fe3O4.Dox were obtained by the Fe3O4 nanoparticle-induced self-assembly of mPEG-SS-NH-graft-PAsp-DA. These magnetic nanomicelles showed spherical shapes with average particle size of about 120 nm measured by dynamic light scattering (DLS). Due to the detachment of PEG shell in the presence of dithiothreitol (DTT), the magnetic nanomicelles showed accelerated in vitro release of Dox, and enhanced cellular uptake ability. Compared with free Dox, the Dox-loaded magnetic nanomicelles showed essential decreased cytotoxicity against Bel-7402 cell line. If its high r2 relaxation rate (221 mM(-1) s(-1)) and good negative contrast effect for magnetic resonance imaging (MRI) were taken into account, mPEG-SS-NH-graft-PAsp-DA@Fe3O4.Dox could be used as MRI-detectable drug carrier of Dox with enhanced cellular uptake ability.
authors.affiliation: Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China. jhyu@sist.ecnu.edu.cn
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Liu
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects*; D052203:Ferrosoferric Oxide / Q000737:chemistry; D006801:Humans; D060328:Magnetic Phenomena; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin; D004298:Dopamine; D052203:Ferrosoferric Oxide