Integrin-Induced Signal Event Contributes to Self-Assembled Monolayers on Au-Nanoparticle-Regulated Cancer Cell Migration and Invasion

ACS Biomater Sci Eng. 2019 Apr 8;5(4):1804-1821. doi: 10.1021/acsbiomaterials.8b01648. Epub 2019 Mar 28.

Abstract

Gold nanoparticles (Au NPs) have received much attention because of their distinct physicochemical properties. The surface terminal functional groups of Au NPs can facilitate easy conjugation with biological molecules for targeting cancer cells and controlling drugs/genes release. However, little is known regarding molecular mechanisms involved in their regulation of cancer cell migration and invasion. In the present study, Au NPs were successfully conjugated with functional groups (CH3, NH2, OH and COOH) by self-assembled monolayer (SAM) technique. The endocytosis of SAM-Au NPs mediating HepG2 cell migration and invasion in integrin-induced cascaded events were examined. Our results showed that the combination of integrins-Caveolin-1 together contributed to the internalization of SAM-Au NPs. The CH3-Au NPs showed fast cell motility than COOH- and OH- groups by upregulating PI3K expression, but reducing FAK phosphorylation level. Additionally, CH3-Au NPs showed the strongest activated GTP-bound Rac1 and RhoA. Taken together, these results concluded that internalization of SAM-Au NPs inhibited cancer cell migration via FAK/PI3K and downstream Rho-GTPase signaling pathway in a time-dependent manner. This work provides a further understanding of SAM-Au NPs regulating cancer cell migration, which might be helpful to functionalize the Au NP surface in drug delivery system.

Keywords: Au nanoparticles (Au NPs); FAK/PI3K; cell migration; integrin; self-assembled monolayers.