Details

Autor(en) / Beteiligte

• Lin, Yao-Xin
• Wang, Yi
• Qiao, Sheng-Lin
• An, Hong-Wei
• Zhang, Ruo-Xin
• Qiao, Zeng-Ying
• Rajapaksha, R. P. Y. J.
• Wang, Lei
• Wang, Hao

Titel

pH-Sensitive Polymeric Nanoparticles Modulate Autophagic Effect via Lysosome Impairment

Ist Teil von

• Small (Weinheim an der Bergstrasse, Germany), 2016-06, Vol.12 (21), p.2921-2931

Ort / Verlag

Germany: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. Using a fluorescent autophagy‐reporting cell, the autophagy‐induced capabilities of four types of pH‐sensitive nanoparticles with variable physiochemical parameters, such as size, surface modification, and pH‐sensitivity are systematically evaluated. The results exhibit that pH‐sensitivity is one of the most important factors in autophagy induction, and that the variation of pH‐sensitivity/concentration of nanoparticles could cause two distinctly different autophagic effects.