title: Inhibition of autophagy overcomes the nanotoxicity elicited by cadmium-based quantum dots.
abstract: Cadmium-based quantum dots (QDs) have shown their values in disease diagnosis, cellular and molecular tracking, small-animal imaging, and therapeutic drug delivery. However, the potential safety problems of QDs, mainly due to their nanotoxicities by unclear mechanisms, have greatly limited its applications. To reverse this situation, we investigated the underlying biological mechanisms of the toxicity of Quantum Dots CdTe/CdS 655 (QDs 655) in this work. QDs 655 was found to elicit nanotoxicity in vitro and in vivo. During the process, autophagy was activated, which was characterized by three main stages of autophagic flux including formation of autophagosomes, lysosomes fused with autophagosomes, and degradation of autophagosomes by lysosomes. Furthermore, the autophagic cell death was demonstrated in vitro under QDs 655 treatment while inhibition of autophagy by pharmacological inhibitors or genetic approaches could attenuate the toxicity induced by QDs 655 in vitro and in vivo. These results indicated that autophagic flux and autophagic cell death were triggered by QDs 655, which elucidated the critical role of autophagy in QDs 655 induced toxicity. Our data may suggest the approach to overcome the toxicity of QDs and other nanoparticles by autophagy inhibition.
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Shaofei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Instrumental Analysis Center, School of Pharmacy, Fudan University, China.
authors.forename: Zhonglian
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Instrumental Analysis Center, School of Pharmacy, Fudan University, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Zongshu
authors.initials: Z
authors.lastname: Xian
authors.affiliation: School of Medicine, Fudan University, China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China.
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University, School of Medicine, Shanghai 200240, China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, China. Electronic address: dianwenju@fudan.edu.cn.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D001343:Autophagy; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D006801:Humans; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D045663:Quantum Dots
chemical_list: D002104:Cadmium
keywords: Autophagy; Biosafety; Cadmium; Nanotoxicity; Quantum dots