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pH, redox and photothermal tri-responsive DNA/polyethylenimine conjugated gold nanorods as nanocarriers for specific intracellular co-release of doxorubicin and chemosensitizer pyronaridine to combat multidrug resistant cancer.

Abstract
Pharmacotherapy of multidrug resistant (MDR) cancer remains a challenging task in clinic. Herein, a pH-responsive DNA and disulfide-linked polyethylenimine functionalized gold nanorod was developed for specific co-delivery of chemotherapeutic agent doxorubicin (DOX) and chemosensitizer pyronaridine (PND) to effectively overcome MDR cancer cells. DOX and PND were firstly carried by a multifunctional nanocomplex for reversing MDR cancer. The nanocomplex can responsively and rapidly release its drugs payload under acidic pH environment (pH, ~5), intracellular GSH concentration content (5 mM) and/or 808 nm NIR laser irradiation. Compared to free DOX, the nanocomplex displayed greatly increased cytotoxicity to MDR MCF-7/ADR cancer cells (IC50, 70.68:6.21 μg/mL). The application of NIR radiation further improved the DOX release and enhanced the antitumor effects of the namomedicine (IC50, drops to 2.88 μg/mL). Consequently, this new nanocomplex exerted greatly increased potency against the MDR cancer cells over free DOX (~20 fold).
AuthorsYun Wang, Zhipeng Zhang, Shaohui Xu, Feihu Wang, Yuanyuan Shen, Shengtang Huang, Shengrong Guo
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 13 Issue 5 Pg. 1785-1795 (07 2017) ISSN: 1549-9642 [Electronic] United States
PMID28185939 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Gold
  • Doxorubicin
  • Polyethyleneimine
  • DNA
Topics
  • Antibiotics, Antineoplastic (administration & dosage, pharmacology)
  • DNA
  • Doxorubicin (administration & dosage, pharmacology)
  • Drug Carriers
  • Gold
  • Humans
  • Hydrogen-Ion Concentration
  • Nanotubes
  • Oxidation-Reduction
  • Polyethyleneimine
  • Tumor Cells, Cultured

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