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  • [Journal of Colloid and Interface Science, 2019] Dual-targeting nanoparticles with core-crosslinked and pH/redox-bioresponsive properties for enhanced intracellular drug delivery
  • 来源:赵军强副教授个人网站 2020-02-25
  • Multifunctional nanoparticles (NPs) with high blood-stability, tumor-targeting ability, and stimuli-bioresponsive drug release behaviors are urgently demanded. Herein, folic acid (FA) and galactose (GAL) functionalized, core-crosslinked NPs (CC NPs) with dual-targeting and pH/redox-bioresponsive properties were developed based on amphiphilic FA-poly(6-O-methacryloyl-d-galactopyranose)-b-poly[2-(diisopropylamino) ethyl methacrylate-co-pyridyl disulfide methylacrylate] [FA-PMAgGP-b-P(DPA-co-PDEMA), termed as FA-PMgDP] block copolymers, and then investigated for facilitated hepatoma-targeting delivery of doxorubicin (DOX). A series of PMgDP copolymers were synthesized though two-step RAFT copolymerization followed by acid-induced acetal deprotection reaction. Their well-defined chemical structures and compositions were characterized by 1H NMR and gel permeation chromatography. Nano-sized, non-crosslinked PMgDP NPs (PMgDP NC NPs) with sizes of less than 25?nm in aqueous solution were self-assembled via the solvent exchange method, and PMgDP CC NPs were readily prepared in the presence of dithiothreitol. The drug-loading content of PMgDP CC NPs was up to 15.8% and its entrapment efficiency was 89.0%. In normal physiological conditions, 11.6% of DOX was released from DOX-loaded PMgDP CC NPs at 25?h, whereas in analogous intracellular microenvironment, 95.5% was released at 11?h owing to the acid-induced protonation of tertiary amine and reductive cleavage of disulfide bond in the hydrophobic core. In a cellular uptake study, FA and GAL-mediated, active, dual-targeted DOX-loaded FA-PMgDP CC NPs showed a 3.54-fold increase in cellular uptake efficiency to HepG2 cells compared to that of shown by single GAL-targeted, DOX-loaded PMgDP NC NPs. Results of in vitro cytotoxicity study showed that blank FA-PMgDP CC NPs exhibited good biocompatibility, whereas dual-targeting DOX-loaded FA-PMgDP CC NPs increased cell apoptosis. Therefore, the above results indicated that the well-constructed FA-PMgDP CC NPs with multi-synergistic effect may serve as new nanocarriers in the field of precise hepatoma-targeting drug delivery.
  • [来源:中国聚合物网]
  • 了解更多请进入: 赵军强副教授个人网站
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