The decrease of PAMAM dendrimer-induced cytotoxicity by PEGylation via attenuation of oxidative stress.
Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers have been widely used in medical applications. However, PAMAM dendrimers bearing amino terminals show certain cytotoxicity. In order to improve their biocompatibility, we modified Generation-5 PAMAM dendrimers by conjugating them with poly(ethylene glycol) (PEG) of two different molecular weights and different number of chains. The IC(50) values of PEGylated dendrimers were 12-105 fold higher than those of PAMAM dendrimers. To investigate the influence of PEGylation on PAMAM-induced cytotoxicity, the intracellular responses, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and apoptosis were examined. The results indicated that conjugation with PEG could effectively reduce the PAMAM-induced cell apoptosis by attenuating the ROS production and inhibiting PAMAM-induced MMP collapse. Meanwhile, dendrimers conjugated with less PEG of lower molecular weight did not significantly change the endocytic properties. Dendrimers conjugated with more PEG of higher molecular weight were much less cytotoxic. This study provided a novel insight into the effects of PEGylation on the decrease of cytotoxicity at the molecular level.
Wang
Wei
W
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China.
Xiong
Wei
W
Wan
Jiangling
J
Sun
Xiaohui
X
Xu
Huibi
H
Yang
Xiangliang
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000633:toxicity*; D050091:Dendrimers; D007928:Lethal Dose 50; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D011073:Polyamines / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000633:toxicity*
D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D011092:Polyethylene Glycols