Disturbance of cellular homeostasis as a molecular risk evaluation of human endothelial cells exposed to nanoparticles.
Paulina WignerKrzysztof ZielinskiSylwia MichlewskaPaulina DanielskaAgnieszka MarczakEduardo Junior RicciRalph Santos-OliveiraMarzena SzwedPublished in: Scientific reports (2021)
Even though application of nanoparticles in medicine seems to provide unique solutions for drug delivery and diagnosis diseases, understanding interactions between nanoscale materials and biological systems is imperative. Therefore, this study determined the effect of different types of nanoparticles (NPs) on human endothelial cells and examined the types of toxicity responses they can induce. Four different types of NPs were tested (PLA/MMT/TRASTUZUMAB, PLA/EDTMP, PLGA/MDP, and Pluronic F127 MICELLES), representing three putative areas of application: anticancer therapy, scintigraphy, and cosmetology. The experiments were performed on immortalized human umbilical vein endothelial cells (HUVEC-STs). Light contrast phase microscopy as well as cell viability assays showed that only Pluronic F127 MICELLES decreased the number of HUVEC-STs in contrast to PLA/MMT/TRASTUZUMAB, PLA/EDTMP, and PLGA/MDP NPs, which altered cell morphology, but not their confluency. The tested NPs induced not only DNA strand-breaks and alkali-labile sites, but also internucleosomal DNA fragmentation, visualized as a DNA ladder pattern typical of apoptosis. Moreover, generation of free radicals and subsequent mitochondrial membrane potential collapse showed the significance of free radical production during interactions between NPs and endothelial cells. High concentrations of NPs had different degrees of toxicity in human endothelial cells and affected cell proliferation, redox homeostasis, and triggered mitochondrial dysfunction.
Keyphrases
- endothelial cells
- high glucose
- drug delivery
- oxide nanoparticles
- oxidative stress
- vascular endothelial growth factor
- drug release
- cell proliferation
- single molecule
- cancer therapy
- magnetic resonance
- circulating tumor
- epidermal growth factor receptor
- cell therapy
- high resolution
- cell free
- magnetic resonance imaging
- computed tomography
- stem cells
- risk assessment
- optical coherence tomography
- induced pluripotent stem cells
- diabetic rats
- atomic force microscopy