期刊
BIOMATERIALS
卷 35, 期 26, 页码 7588-7597出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.05.029
关键词
PAMAM dendrimers; Autophagy; Cell death; Neurotoxicity
资金
- Shanghai Science and Technology Funds [11431920104]
- National Science and Technology Major Project for Drug Discovery of Ministry of Science and Technology of China [2011ZX09102-001-27]
- National Key Basic Research Program of China [2013CB932502]
- School of Pharmacy, Fudan University & The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University)
- Ministry of Education, China [SDD2013-02]
Poly(amidoamine) (PAMAM) dendrimers, are among the most common classes of dendrimers that are intended for a wide range of biomedical applications and extensively investigated for brain-specific drug delivery, imaging and diagnosis. Unfortunately, neurotoxicity of PAMAM dendrimers, the underlying mechanism of which is poorly-elucidated, poses a far-reaching challenge to their practical applications. In this study, we reported that PAMAM dendrimers induced both cytotoxicity and autophagic flux in a panel of human glioma cell lines. Meanwhile, inhibition of autophagy significantly reversed cell death caused by PAMAM dendrimers, indicating the cytotoxic role of autophagy in neurotoxicity caused by PAMAM dendrimers. Akt/mTOR pathway was most likely to participate in initiation of PAMAM dendrimers-induced autophagy. Moreover, autophagy induced by PAMAM dendrimers might be partially mediated by intracellular ROS generation. Collectively, these data elucidated the critical role of autophagy in neurotoxicity associated with exposure to cationic PAMAM dendrimers in vitro, raising concerns about possible neurotoxic reaction caused by future clinical applications of PAMAM dendrimers and providing potential strategies to ameliorate toxic effects of PAMAM dendrimers. (C) 2014 Elsevier Ltd. All rights reserved.
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