Stimuli-responsive PEGylated prodrugs for targeted doxorubicin delivery

Materials Science & Engineering. C, Materials for Biological Applications
Minghui XuHongjie Wang

Abstract

In recent years, stimuli-sensitive prodrugs have been extensively studied for the rapid "burst" release of antitumor drugs to enhance chemotherapeutic efficiency. In this study, a novel stimuli-sensitive prodrug containing galactosamine as a targeting moiety, poly(ethylene glycol)-doxorubicin (PEG-DOX) conjugate, was developed for targeting HepG2 human liver cancer cells. To obtain the PEG-DOX conjugate, both galactosamine-decorated poly(ethylene glycol) aldehyde (Gal-PEG-CHO) and methoxy poly(ethylene glycol) aldehyde (mPEG-CHO) were firstly synthesized and functionalized with dithiodipropionate dihydrazide (TPH) through direct reductive amination via Schiff's base formation, and then DOX molecules were chemically conjugated to the hydrazide end groups of TPH-functionalized Gal-/m-PEG chains via pH-sensitive hydrazone linkages. The chemical structures of TPH-functionalized PEG and PEG-DOX prodrug were confirmed by (1)H NMR analysis. The PEG-DOX conjugate could self-assemble into spherical nanomicelles with a mean diameter of 140 nm, as indicated by transmission electron microscopy and dynamic light scattering. The drug loading content and loading efficiency in the prodrug nanomicelles were as high as 20 wt.% and 75 wt.%, respe...Continue Reading

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Citations

Aug 15, 2017·Journal of Drug Targeting·Juan LiRongmei Wang
Apr 28, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yixiao GuoLiqin Xiong
Mar 3, 2017·Journal of Materials Science. Materials in Medicine·Y DanyuoW O Soboyejo
Jul 3, 2020·Colloids and Surfaces. B, Biointerfaces·Qingqing PanBin He
Mar 18, 2021·Annual Review of Chemical and Biomolecular Engineering·Souvik GhosalChristopher A Alabi
Mar 14, 2018·Chemical Reviews·Farzad SeidiDaniel Crespy

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