title: Cardiovascular toxicity assessment of poly (ethylene imine)- based cationic polymers on zebrafish model.
abstract: Poly(ethylene imine)s (PEIs) have gained enormous attention in designing novel drug delivery systems for cancer treatment. High molecular weight of PEIs such as PEI 25 kD are promising for their drug carrying capacity. However, increased molecular weight is associated with toxicity. Currently, the toxicity evaluation of PEIs is mainly focused on the culture cell models, with very few studies investigating the risk assessment in vivo. Herein, the systemic evaluation of branched PEI 25 kD and PEI-CyD (PC) composed of low molecular PEI (Mw 600) and β-cyclodextrin (β-CyD) is performed in zebrafish model and endothelial cells. Our finding indicate that exposure of PC and PEI 25 kD can induce high mortality rate, shorten hatching time, promote malformations and cell apoptosis of zebrafish embryos in a dose-dependent manner. Most significantly, the cationic polymer PC and PEI 25 kD can decrease heart rate of zebrafish embryos and down-regulate the expression of heart development-related genes, which demonstrate their cardiovasculature toxicity. In this case, we further investigate the effect of PC on endothelial cells. Indeed, PC can induce endothelial cells dysfunction, including oxidative stress and apoptosis which are involved in cardiovascular diseases. These fundamental studies provide valuable insights into the biocompatible evaluation of PEI based drug carriers.
authors.affiliation: a College of Biotechnology and Bioengineering , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: a College of Biotechnology and Bioengineering , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Fengliang
authors.initials: F
authors.lastname: Guo
authors.affiliation: a College of Biotechnology and Bioengineering , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Fenghui
authors.initials: F
authors.lastname: Zhao
authors.affiliation: b Institute of Chemical Biology and Pharmaceutical Chemistry , Zhejiang University , Hangzhou , China.
authors.forename: Guping
authors.initials: G
authors.lastname: Tang
authors.affiliation: a College of Biotechnology and Bioengineering , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007097:Imines / Q000737:chemistry* / Q000633:toxicity*; D008422:Materials Testing; D051379:Mice; D011095:Polyethylenes / Q000737:chemistry* / Q000633:toxicity*; D000067996:RAW 264.7 Cells; D015027:Zebrafish
chemical_list: D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine)
keywords: Cationic polymer; PEI; cardiovascular toxicity; endothelial cells; zebrafish