Small gold nanoparticles presenting linear and looped Cilengitide analogues as radiosensitizers of cells expressing α_νβ₃ integrin

This work uses linear and looped RGDfV sequences attached to the surface of small (1.8 nm in diameter) gold nanoparticles (AuNPs) to enhance the radiosensitizating effects of Cilengitide, a cyclic RGDf (NMe)V pentapeptide that targets α_vβ₃ integrin which is overexpressed in certain cancers. Following synthesis and purification, the AuNPs were evaluated in vitro against HUVEC, H460, and MCF7 cells in clonogenic assays using a ¹³⁷Cs irradiator. Untargeted AuNPs induced no significant dose enhancement factors (DEFs) in any of the cell types when compared to radiation treatment alone, whereas all evaluated AuNPs functionalized with targeting peptides performed at least as well as controls (irradiation after Cilengitide treatment). The observed DEFs also suggest that cyclizing the linear peptides into more spatially constrained, looped structures may facilitate target binding. These greater dose enhancements merit future in vivo studies of drug-AuNP conjugates to assess the ability of the nanostructures to provide an improved therapeutic benefit over treatment with drug candidates and radiation alone.