PMID- 27422748 OWN - NLM STAT- MEDLINE DCOM- 20170208 LR - 20170208 IS - 1742-7843 (Electronic) IS - 1742-7835 (Linking) VI - 120 IP - 1 DP - 2017 Jan TI - Thermoresponsive Polymers with Lower Critical Solution Temperature- or Upper Critical Solution Temperature-Type Phase Behaviour Do Not Induce Toxicity to Human Endothelial Cells. PG - 79-85 LID - 10.1111/bcpt.12643 [doi] AB - Thermoresponsive polymers have gained extensive attention as biomedical materials especially for targeted drug delivery systems. We have recently developed water-soluble polypeptide-based thermoresponsive polymers that exhibit lower critical solution temperature (LCST)- or upper critical solution temperature (UCST)-type phase behaviours. In this study, the toxicity of these polymers to human umbilical vein endothelial cells (HUVECs) was investigated to assess the safety and biocompatibility. Up to 100 mug/ml, thermoresponsive polymers did not induce cytotoxicity to HUVECs, showing as unaltered mitochondrial viability assessed as cell counting kit-8 (CCK-8) assay and membrane integrity assessed as lactate dehydrogenase (LDH) assay. Inflammatory response, assessed as the release of chemokine-soluble monocyte chemotactic protein 1 (sMCP-1) and interleukin-8 (IL-8) as well as cytokine IL-6, was not significantly affected by the polymers. In addition, 1 muM thapsigargin (TG), an endoplasmic reticulum (ER) stress inducer, significantly decreased mitochondrial viability, but did not affect membrane integrity or inflammatory response. The presence of thermoresponsive polymers with LCST-type phase behaviour did not further affect the effects of TG. In conclusion, the thermoresponsive polymers used in this study are not toxic to endothelial cells and therefore could be further considered as safe materials for biomedical applications. CI - (c) 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). FAU - Ji, Yuejia AU - Ji Y AD - Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China. FAU - Zhu, Mengxiang AU - Zhu M AD - Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, Key Laboratory of Advanced Functional Polymer Materials of Colleges and Universities of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China. FAU - Gong, Yu AU - Gong Y AD - Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China. FAU - Tang, Haoyu AU - Tang H AD - Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, Key Laboratory of Advanced Functional Polymer Materials of Colleges and Universities of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China. FAU - Li, Juan AU - Li J AD - Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China. FAU - Cao, Yi AU - Cao Y AD - Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20160805 PL - England TA - Basic Clin Pharmacol Toxicol JT - Basic & clinical pharmacology & toxicology JID - 101208422 RN - 0 (Biocompatible Materials) RN - 0 (Cytokines) RN - 0 (Enzyme Inhibitors) RN - 0 (Peptides) RN - 0 (Polymers) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Biocompatible Materials/*adverse effects/chemistry MH - Body Temperature MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cytokines/metabolism MH - Drug Delivery Systems/*adverse effects MH - Endoplasmic Reticulum Stress/drug effects MH - Endothelium, Vascular/cytology/*drug effects/immunology/metabolism MH - Enzyme Inhibitors/toxicity MH - Human Umbilical Vein Endothelial Cells/cytology MH - Humans MH - Materials Testing MH - Peptides/*adverse effects/chemistry MH - Polymers/*adverse effects/chemistry MH - Solubility MH - Thapsigargin/toxicity MH - Transition Temperature EDAT- 2016/07/17 06:00 MHDA- 2017/02/09 06:00 CRDT- 2016/07/17 06:00 PHST- 2016/03/09 00:00 [received] PHST- 2016/07/13 00:00 [accepted] PHST- 2016/07/17 06:00 [pubmed] PHST- 2017/02/09 06:00 [medline] PHST- 2016/07/17 06:00 [entrez] AID - 10.1111/bcpt.12643 [doi] PST - ppublish SO - Basic Clin Pharmacol Toxicol. 2017 Jan;120(1):79-85. doi: 10.1111/bcpt.12643. Epub 2016 Aug 5.