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Trafficking microenvironmental pHs of polycationic gene vectors in drug-sensitive and multidrug-resistant MCF7 breast cancer cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
9240 622 2010 8 PDF Available
Title
Trafficking microenvironmental pHs of polycationic gene vectors in drug-sensitive and multidrug-resistant MCF7 breast cancer cells
Abstract

While multidrug resistance (MDR) has been a significant issue in cancer chemotherapy, delivery resistance to various anti-cancer biotherapeutics, including genes, has not been widely recognized as a property of MDR. This study aims to provide a better understanding of the transfection characteristics of drug-sensitive and drug-resistant cells by tracing microenvironmental pHs of two representative polymer vectors: poly(l-lysine) and polyethyleneimine. Drug-sensitive breast MCF7 cells had four- to seven-times higher polymeric transfection efficiencies than their counterpart drug-resistant MCF7/ADR-RES cells. Polyplexes in MCF7/ADR-RES cells after endocytosis were exposed to a more acidic microenvironment than those in MCF7 cells; the MDR cells show faster acidification rates in endosomes/lysosomes than the drug-sensitive cells after endocytosis (in the case of PLL/pDNA complexes, ∼ pH 5.1 for MCF7/ADR-RES cells vs. ∼ pH 6.8 for MCF7 cells at 0.5 h post-transfection). More polyplexes were identified trapped in acidic subcellular compartments of MCF7/ADR-RES cells than in MCF7 cells, suggesting that they lack endosomal escaping activity. These findings demonstrate that the design of polymer-based gene delivery therapeutics should take into account the pH of subcellular compartments.

Keywords
Multidrug resistance; pH trafficking; Polyethyleneimine; Poly(l-lysine); Polymeric gene delivery; Solid tumors
First Page Preview
Trafficking microenvironmental pHs of polycationic gene vectors in drug-sensitive and multidrug-resistant MCF7 breast cancer cells
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 11, April 2010, Pages 3071–3078
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering