pH-Sensitive Polymeric Nanoparticles Modulate Autophagic Effect via Lysosome Impairment.
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.
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.|University of Chinese Academy of Science (UCAS), No.19A Yuquan Road, Beijing, China.
Yao-Xin
YX
Lin
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.|University of Chinese Academy of Science (UCAS), No.19A Yuquan Road, Beijing, China.
Yi
Y
Wang
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.|University of Chinese Academy of Science (UCAS), No.19A Yuquan Road, Beijing, China.
Sheng-Lin
SL
Qiao
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.|University of Chinese Academy of Science (UCAS), No.19A Yuquan Road, Beijing, China.
Hong-Wei
HW
An
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.
Ruo-Xin
RX
Zhang
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.
Zeng-Ying
ZY
Qiao
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.
R P Y J
RP
Rajapaksha
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.
Lei
L
Wang
CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.
Hao
H
Wang
D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000737:chemistry*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*
D004337:Drug Carriers; D011108:Polymers
autophagy; cancer; lysosome; nanoparticles; pH-sensitive