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Self-reinforced endocytoses of smart polypeptide nanogels for "on-demand" drug delivery.

Abstract
The pH and reduction dual-responsive polypeptide nanogels with self-reinforced endocytoses were prepared through ring-opening polymerization of l-glutamate N-carboxyanhydrides, deprotection of benzyl group and subsequent quaternization reaction between γ-2-chloroethyl-l-glutamate unit in polypeptide block and 2,2'-dithiobis(N,N-dimethylethylamine). The nanogels were revealed to exhibit smart pH and reduction dual-responsiveness, and excellent biocompatibilities, which expressed great potential as antitumor drug nanocarriers. Doxorubicin (DOX) as a model antitumor drug was loaded into nanogels through dispersion. DOX-loaded nanogels displayed a stable core-cross-linked structure under normal physiological condition (pH7.4), while rapidly releasing the payloads in the mimicking endosomal (pH5.3), tumor tissular (pH6.8) or intracellular reductive microenvironments (10.0mM glutathione). Confocal fluorescence microscopy demonstrated that DOX-loaded nanogels could deliver DOX into HepG2 cells (a human hepatoma cell line) more efficiently than the parent DOX-loaded micelle and free DOX. The enhanced cellular internalizations of DOX-loaded nanogels were more significant under tumor tissular acidic condition (pH6.8) ascribed to the quaternary ammonium groups in the cores. In addition, DOX-loaded nanogels exhibited improved in vitro and in vivo antitumor activities, and in vivo securities compared with DOX-loaded micelle and free DOX. These excellent features of the smart nanogels with quaternary ammonium groups were endowed with a bright prospect for intracellular targeting antitumor drug delivery.
AuthorsJianxun Ding, Weiguo Xu, Ying Zhang, Diankui Sun, Chunsheng Xiao, Donghong Liu, Xiaojuan Zhu, Xuesi Chen
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 172 Issue 2 Pg. 444-55 (Dec 10 2013) ISSN: 1873-4995 [Electronic] Netherlands
PMID23742879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Ethylamines
  • NanoGel
  • Peptides
  • Polyethylene Glycols
  • N,N-dimethylethylamine
  • Doxorubicin
  • Polyethyleneimine
Topics
  • Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
  • Doxorubicin (administration & dosage, pharmacokinetics)
  • Drug Carriers (chemistry, metabolism)
  • Drug Delivery Systems
  • Endocytosis
  • Ethylamines (chemistry, metabolism)
  • Hep G2 Cells
  • Humans
  • Peptides (chemistry, metabolism)
  • Polyethylene Glycols (chemistry, metabolism)
  • Polyethyleneimine (chemistry, metabolism)
  • Polymerization

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