Sorafenib derivatives-functionalized gold nanoparticles confer protection against tumor angiogenesis and proliferation via suppression of EGFR and VEGFR-2

Exp Cell Res. 2021 Jun 2:112633. doi: 10.1016/j.yexcr.2021.112633. Online ahead of print.ABSTRACTIncreasing evidence has reported the great promise of multicomponent and multifunctional nanoparticles as advanced therapies of human diseases, especially tumors. In the current study, we investigated the functionality of new sorafenib derivatives-capped gold nanoparticles (AuNPs-New Sor) in tumor growth as well as their anti-tumor mechanisms. Initially, new sorafenib derivatives were constructed and combined with AuNPs to form AuNPs-New Sor. the properties of synthesized AuNPs-New Sor were identified in a mouse model of tumorigenesis. The effect of AuNPs-New Sor on tumor vascular normalization was investigated by assessing vascular permeability and perfusion rate while the molecular mechanism was characterized by measuring the expression of epithelial-mesenchymal transition (EMT) makers, and vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2). Next, we evaluated effect of AuNPs-New Sor on migration and proliferation of tumor cells and human umbilical vein endothelial cells (HUVECs) and angiogenesis of HUVECs as well as it antitumor activity in vivo. Compounds 10b, 10m and 10q showed in vitro inhibitory activities against EGFR and VEGFR-2, and anti-proliferative activities against HCT116, MCF-7 and B16F10 cell lines, among which Compound 10q exhibit better effect and hence was selected to form AuNPs-New Sor. AuNPs could deliver new sorafenib derivatives into tumor...
Source: Experimental Cell Research - Category: Cytology Authors: Source Type: research