title: Interplay of Oxidative Stress and Autophagy in PAMAM Dendrimers-Induced Neuronal Cell Death.
abstract: Poly-amidoamine (PAMAM) dendrimers are proposed to be one of the most promising drug-delivery nanomaterials. However, the toxicity of PAMAM dendrimers on the central nervous system seriously hinders their medical applications. The relationship between oxidative stress and autophagy induced by PAMAM dendrimers, and its underlying mechanism remain confusing. In this study, we reported that PAMAM dendrimers induced both reactive oxygen species and autophagy flux in neuronal cells. Interestingly, autophagy might be triggered by the formation of reactive oxygen species induced by PAMAM dendrimers. Suppression of reactive oxygen species could not only impair PAMAM dendrimers-induced autophagic effects, but also reduce PAMAM dendrimers-induced neuronal cell death. Moreover, inhibition of autophagy could protect against PAMAM dendrimers-induced neuronal cell death. These findings systematically elucidated the interplay between oxidative stress and autophagy in the neurotoxicity of PAMAM dendrimers, which might encourage the application of antioxidants and autophagy inhibitors to ameliorate the neurotoxicity of PAMAM dendrimers in clinic.
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Shaofei
authors.initials: S
authors.lastname: Wang
authors.affiliation: 2. Shanghai Animal Disease Control Center, Shanghai 201103, P.R. China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Qian
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Fan
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: 3. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Xuesai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 4. Department of Pharmaceutics & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.affiliation: 1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D000818:Animals; D001343:Autophagy; D001672:Biocompatible Materials / Q000633:toxicity*; D016923:Cell Death; D002460:Cell Line; D050091:Dendrimers / Q000633:toxicity*; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D017382:Reactive Oxygen Species
keywords: Autophagy; Nanomaterials; Neuronal cell; Oxidative stress