Theranostics 2015; 5(12):1363-1377. doi:10.7150/thno.13181

Research Paper

Interplay of Oxidative Stress and Autophagy in PAMAM Dendrimers-Induced Neuronal Cell Death

Yubin Li1#, Haiyan Zhu1#, Shaofei Wang1#, Xiaolu Qian2, Jiajun Fan1, Ziyu Wang1, Ping Song1, Xuesai Zhang3, Weiyue Lu4, Dianwen Ju1✉

1. Department of Biosynthesis & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China
2. Shanghai Animal Disease Control Center, Shanghai 201103, P.R. China
3. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China
4. Department of Pharmaceutics & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China
# Yubin Li, Haiyan Zhu, and Shaofei Wang contributed equally to this work.

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.

Keywords: Oxidative stress, Autophagy, Nanomaterials, Neuronal cell

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How to cite this article:
Li Y, Zhu H, Wang S, Qian X, Fan J, Wang Z, Song P, Zhang X, Lu W, Ju D. Interplay of Oxidative Stress and Autophagy in PAMAM Dendrimers-Induced Neuronal Cell Death. Theranostics 2015; 5(12):1363-1377. doi:10.7150/thno.13181. Available from http://www.thno.org/v05p1363.htm