Journal
BIOMATERIALS
Volume 32, Issue 33, Pages 8613-8625Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.07.047
Keywords
Biocompatibility; Polyethylenimine; Autophagy; Necrosis; Apoptosis; Cytotoxicity
Funding
- National Natural Science Foundation of China [30801442, 30801439, 81072592]
- National Key Basic Research Program [2010CB529800, 2007CB935800]
- SRF for ROCS, SEM
- Shanghai Municipal Education Commission
- Shanghai Science and Technology Committee [10QA1404100]
Ask authors/readers for more resources
Polyethylenimine (PEI) is one of the most effective and widely used cationic macromolecules in experimental gene transfer/therapy protocols. However, the further clinical application of PEI is largely impeded by its cytotoxicity. Here we performed a fundamental investigation on the mechanism of PEI-induced cytotoxicity in both hepatic and nephritic cell lines. It was demonstrated that besides necrosis and apoptosis, autophagy was apparently associated with PEI-induced cytotoxicity and contributed to aggravated cell damage. Specifically, at the early stage (3 h) of PEI-induced cytotoxicity, autophagy was mainly correlated with lysosome damage, but in the later phase (after a 24-h recovery), autophagy was mainly related with mitochondrial injury. Modulation of Rab5, Rab7 expression and inhibition of clathrin-mediated endocytosis pathway significantly affected the formation of autophagosome, which suggested that the endolysosome transport pathway especially the clathrin-mediated endocytosis at least partly facilitated PEI-induced autophagy. As PEI-induced autophagy played a causative role in its cytotoxicity, it's highly recommended to design PEI-based gene-carriers that could avoid the endolysosome transport pathway. (C) 2011 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available