Poly (L-γ-glutamylglutamine) nanoparticles enhance drug accumulation in resistant cells

Abstract

Abstract: This work investigated the antitumor efficacy of poly (L-γ-glutamylglutamine) (PGG) prodrug in multidrug resistant (MDR) cancer cells and the possible mechanisms. The A549 cell line was induced to become multidrug resistant. A549 was applied to evaluate the effect of PGG-Dox on intracellular accumulation and retention of Dox. Endocytosis inhibition studies and transmission electron microscope assay were used to investigate the mechanisms of cellular PGG-Dox uptake. Confocal laser scanning microscopy was performed to confirm the drug accumulation. Treatment of MDR cells with PGG-Dox resulted in significantly enhanced drug accumulation and retention after the end of treatment compared with free Dox. Endocytosis inhibition studies showed pinocytosis is the mainly pathway in the elevated membrane permeability of the PGG-Dox. These demonstrated that Dox conjugate with PGG NPs effectively bypass the multidrug resistance. Our PGG DDS may be considered as an attractive and promising delivery system to overcome multidrug resistance.

Key words: multidrug resistance, polymer drug delivery system, nanotechnology, nanomedicine

CLC Number:

LIU Kai, CHEN Jing, WANG Jing, YU Lei, ZHU Jian-zhong, WANG Yi-ting. Poly (L-γ-glutamylglutamine) nanoparticles enhance drug accumulation in resistant cells[J]. Journal of East China Normal University(Natural Sc, 2013, 2013(6): 141-149.

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