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A nuclear targeted Dox-aptamer loaded liposome delivery platform for the circumvention of drug resistance in breast cancer.

Abstract
The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs in the cytoplasm from the cell, is a major mechanism of MDR. Nuclear-targeted nanoparticle drug delivery system, which enables intranuclear release of anticancer drugs, is expected to address this challenge. In this study, based on nucleolin's active transport property to the nucleus and its affinity with aptamer, we developed a nuclear-targeted delivery system to circumvention of drug resistance in breast cancer (MCF-7/Adr). Dox·HCl inserted in the aptamer AS1411 (Ap-Dox) was encapsulated in the aqueous interior of liposome (Lip(Ap-Dox)). In vitro studies showed that after the Lip(Ap-Dox) diffusing into MCF-7/Adr cells, Ap-Dox complex bound with nucleolin strongly and eventually entered the cell nuclei. By using this drug delivery system, Dox·HCl can efficiently accumulated in the nuclei to effectively kill the cancer cells.
AuthorsXin Li, Xiuhua Wu, Hongyu Yang, Lin Li, Ziqi Ye, Yuefeng Rao
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 117 Pg. 109072 (Sep 2019) ISSN: 1950-6007 [Electronic] France
PMID31202169 (Publication Type: Journal Article)
CopyrightCopyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • Aptamers, Nucleotide
  • Liposomes
  • Phosphoproteins
  • RNA-Binding Proteins
  • Doxorubicin
Topics
  • Aptamers, Nucleotide (chemistry)
  • Breast Neoplasms (drug therapy, pathology)
  • Cell Death (drug effects)
  • Cell Nucleus (metabolism)
  • Doxorubicin (pharmacology, therapeutic use)
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm (drug effects)
  • Endocytosis (drug effects)
  • Female
  • Humans
  • Liposomes
  • MCF-7 Cells
  • Phosphoproteins (metabolism)
  • RNA-Binding Proteins (metabolism)
  • Nucleolin

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