Effects of Gold Nanoparticles on Capillary Tube Formation with Special Reference to the Alteration of Pericyte Morphology and Function

Abstract

Pericytes are perivascular cells that wrap around endothelial cells to form wall of capillaries and post‐capillary venules. These cells are primary importance in physiological and pathological processes, especially, involved in angiogenesis. At present, gold nanoparticles (AuNPs) were used for anti‐angiogenesis by inhibiting the activity of endothelial cell proliferation, migration, and tube formation. However, the effects of gold nanoparticles on the alteration of pericyte morphology and theirs function were not reported. Therefore, in this study, 20 nm‐AuNPs were applied to human placenta pericyte monoculture with concentration of 30 ppm. Morphology of pericytes was observed by transmission electron microscopy and cell migration was evaluated by transwell migration assay. Real‐time qRT‐PCR was used to determine Ki‐67, as a proliferation marker, and PDGFR‐β mRNA expression. Moreover, these AuNPs 30 ppm‐treated pericytes were co‐cultured with human umbilical cord endothelial cells on Matrigel® to investigate the 3D tube formation. The results revealed that AuNPs significantly suppressed migration, proliferation, and PDGFR‐β mRNA expression of pericytes. The ultrastructure of pericytes showed AuNPs in several organelles, i.e., swollen or damaged mitochondria, engulfed late endosomes and lysosomes. Moreover, the number of capillary tube formations was essentially reduced and we found that a number of pericytes on these capillary tubes were round shape and did not extend the processes along the tube, which in turn increased incomplete tube formation compared with the control. In conclusion, AuNPs could effect on pericyte biology including proliferation, migration, morphology, and tube formation property. Moreover, the results highlighted the potential application of AuNPs in anti‐angiogenesis by pericyte‐targeted therapy.Support or Funding InformationThe Ratchadaphiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number RA61/100 and Overseas Academic Presentation Scholarship for Graduate Students from the Graduate School, Chulalongkorn University