title: Thermoresponsive Polymers with Lower Critical Solution Temperature- or Upper Critical Solution Temperature-Type Phase Behaviour Do Not Induce Toxicity to Human Endothelial Cells.
abstract: 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 μg/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 μM 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.
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China.
authors.forename: Yuejia
authors.initials: Y
authors.lastname: Ji
authors.affiliation: 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.
authors.forename: Mengxiang
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gong
authors.affiliation: 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.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Tang
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Environment-Friendly Chemistry and Applications Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, Hunan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
mesh_terms: D001672:Biocompatible Materials / Q000009:adverse effects* / Q000737:chemistry; D001831:Body Temperature; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D008422:Materials Testing; D010455:Peptides / Q000009:adverse effects* / Q000737:chemistry; D011108:Polymers / Q000009:adverse effects* / Q000737:chemistry; D012995:Solubility; D019284:Thapsigargin / Q000633:toxicity; D044366:Transition Temperature
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D004791:Enzyme Inhibitors; D010455:Peptides; D011108:Polymers; D019284:Thapsigargin