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.