PMID- 28025169 OWN - NLM STAT- MEDLINE DCOM- 20170201 LR - 20181202 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 263 DP - 2017 Feb 1 TI - Evaluation of in vitro toxicity of polymeric micelles to human endothelial cells under different conditions. PG - 46-54 LID - S0009-2797(16)30435-5 [pii] LID - 10.1016/j.cbi.2016.12.014 [doi] AB - 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 mug/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. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Liu, Fang AU - Liu F AD - Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China. FAU - Huang, Haikang AU - Huang H AD - 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. FAU - Gong, Yu AU - Gong Y AD - Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China. FAU - Li, Juan AU - Li J AD - Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China. FAU - Zhang, Xuefei AU - Zhang X AD - 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. FAU - Cao, Yi AU - Cao Y AD - 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. LA - eng PT - Journal Article DEP - 20161223 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (Drug Carriers) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Micelles) RN - 0 (Palmitates) RN - 0 (Polyesters) RN - 0 (Reactive Oxygen Species) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (methoxy poly(ethylene glycol)-poly(lactide)) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Cell Adhesion/drug effects MH - Cell Line MH - Drug Carriers/chemistry/toxicity MH - Endoplasmic Reticulum Stress/*drug effects MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Interleukin-6/metabolism MH - Interleukin-8/metabolism MH - *Micelles MH - Monocytes/cytology/immunology MH - Palmitates/toxicity MH - Polyesters/chemistry/*toxicity MH - Polyethylene Glycols/chemistry/*toxicity MH - Reactive Oxygen Species/metabolism MH - Thapsigargin/toxicity MH - Vascular Cell Adhesion Molecule-1/metabolism OTO - NOTNLM OT - Human umbilical vein endothelial cells (HUVECs) OT - Methoxy-poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA) OT - Micelles OT - Palmitate (PA) OT - Thapsigargin (TG) EDAT- 2016/12/28 06:00 MHDA- 2017/02/02 06:00 CRDT- 2016/12/28 06:00 PHST- 2016/10/06 00:00 [received] PHST- 2016/12/16 00:00 [revised] PHST- 2016/12/22 00:00 [accepted] PHST- 2016/12/28 06:00 [pubmed] PHST- 2017/02/02 06:00 [medline] PHST- 2016/12/28 06:00 [entrez] AID - S0009-2797(16)30435-5 [pii] AID - 10.1016/j.cbi.2016.12.014 [doi] PST - ppublish SO - Chem Biol Interact. 2017 Feb 1;263:46-54. doi: 10.1016/j.cbi.2016.12.014. Epub 2016 Dec 23.