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.
Colloids Surf B Biointerfaces. 2013 Jul 1;107:213-9. doi: 10.1016/j.colsurfb.2013.02.009. Epub 2013 Feb 26.
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.
本研究旨在开发一种聚乙二醇(PEG)可脱落的磁性纳米胶束作为阿霉素(Dox)的载体,以增强其细胞摄取能力,并实现同步磁共振成像(MRI)可见功能。首先,通过末端为氨基的二硫键连接的聚乙二醇单甲醚(mPEG-SS-NH2)和多巴胺(DA)将聚(L-琥珀酰亚胺)(PSI)中的五元环依次开环,生成 mPEG-SS-NH-接枝-PAsp-DA 接枝共聚物。然后,通过 Fe3O4 纳米粒子诱导 mPEG-SS-NH-接枝-PAsp-DA 的自组装,得到载药的 mPEG-SS-NH-接枝-PAsp-DA@Fe3O4.Dox 磁性纳米胶束。这些磁性纳米胶束呈球形,通过动态光散射(DLS)测量,平均粒径约为 120nm。由于在二硫苏糖醇(DTT)存在下 PEG 壳的脱落,磁性纳米胶束表现出加速的体外 Dox 释放,并增强了细胞摄取能力。与游离 Dox 相比,载药磁性纳米胶束对 Bel-7402 细胞系的细胞毒性显著降低。如果考虑到其高 r2 弛豫率(221mM-1s-1)和对磁共振成像(MRI)的良好负对比效应,mPEG-SS-NH-接枝-PAsp-DA@Fe3O4.Dox 可作为具有增强细胞摄取能力的 Dox 的 MRI 检测药物载体。
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