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pH‐Sensitive Polymeric Nanoparticles Modulate Autophagic Effect via Lysosome Impairment
Author(s) -
Lin YaoXin,
Wang Yi,
Qiao ShengLin,
An HongWei,
Zhang RuoXin,
Qiao ZengYing,
Rajapaksha R. P. Y. J.,
Wang Lei,
Wang Hao
Publication year - 2016
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201503709
Subject(s) - autophagy , lysosome , nanoparticle , drug delivery , pi3k/akt/mtor pathway , cell culture , nanotechnology , programmed cell death , materials science , microbiology and biotechnology , biophysics , chemistry , apoptosis , biochemistry , biology , enzyme , genetics
In drug delivery systems, pH‐sensitive polymers are commonly used as drug carriers, and significant efforts have been devoted to the aspects of controlled delivery and release of drugs. However, few studies address the possible autophagic effects on cells. Here, for the first time, using a fluorescent autophagy‐reporting cell line, this study evaluates the autophagy‐induced capabilities of four types of pH‐sensitive polymeric nanoparticles (NPs) with different physical properties, including size, surface modification, and pH‐sensitivity. Based on experimental results, this study concludes that pH‐sensitivity is one of the most important factors in autophagy induction. In addition, this study finds that variation of concentration of NPs could cause different autophagic effect, i.e., low concentration of NPs induces autophagy in an mTOR‐dependent manner, but high dose of NPs leads to autophagic cell death. Identification of this tunable autophagic effect offers a novel strategy for enhancing therapeutic effect in cancer therapy through modulation of autophagy.

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