title: Evaluation of in vitro toxicity of polymeric micelles to human endothelial cells under different conditions.
abstract: Polymeric micelles have been extensively studied in the area of antitumor therapy, and more recently explored as nanocarriers for atherosclerosis. These applications of polymeric micelles in biomedicine will increase their contact with human blood vessels. However, few studies have considered the interactions between polymeric micelles and endothelial cells, especially in a complex system. This study used human umbilical vein endothelial cells (HUVECs) as an in vitro model for endothelial cells to investigate the toxic effects of methoxy-poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) based micelles. In addition, an endoplasmic reticulum stress inducer thapsigargin (TG), and a pro-atherogenic stimulus palmitate (PA), were used to co-expose HUVECs to further mimic the responses of diseased endothelial cells to micelle exposure. Overall, up to 200 μg/mL micelles did not significantly induce cytotoxicity, reactive oxygen species (ROS), release of inflammatory mediators in terms of interleukin 6 (IL-6), IL-8 and soluble vascular cell adhesion molecule 1 (sVCAM-1), or adhesion of THP-1 monocytes to HUVECs. TG and PA significantly induced cytotoxicity and THP-1 adhesion as well as modestly promoted the release of IL-6, but did not affect ROS or release of sVCAM-1 and IL-8. Co-exposure of micelles did not significantly enhance the effects of TG and PA to HUVECs, and ANOVA analysis indicated no interaction between concentrations of micelles and the presence of TG/PA. Taken together, these data indicated that micelles are not toxic to HUVECs under different conditions in vitro.
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Key Laboratory of Advanced Functional Polymeric Materials of College of Hunan Province and Key Laboratory of Polymeric Materials & Application Technology of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
authors.forename: Haikang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Key Laboratory of Advanced Functional Polymeric Materials of College of Hunan Province and Key Laboratory of Polymeric Materials & Application Technology of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan 411105, China. Electronic address: zxf7515@163.com.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China. Electronic address: caoyi39@xtu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008823:Micelles; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010168:Palmitates / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019284:Thapsigargin / Q000633:toxicity; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D015850:Interleukin-6; D016209:Interleukin-8; D008823:Micelles; D010168:Palmitates; D011091:Polyesters; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D019284:Thapsigargin
keywords: Human umbilical vein endothelial cells (HUVECs); Methoxy-poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA); Micelles; Palmitate (PA); Thapsigargin (TG)