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 αvβ3 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.
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Dose enhancement factors
Non-small cell lung carcinoma
Vascular endothelial growth factor
Enhanced permeability and retention
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We thank the Vanderbilt Institute of Nanoscale Science and Engineering for use of the TGA and TEM instruments for particle characterization. We would also like to thank Dr. Michael Freeman of Vanderbilt University Medical Center for access to irradiation facilities. Finally, we would like to express our gratitude for the editorial assistance given by Shellie Richards in the preparation of this manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Experimental methods detailing the synthesis of the Cilengitide mimic, characterization data (1H NMR, TEM, and TGA) of the AuNPs, and procedures for the place exchange and EDC/NHS coupling reactions can be found in the online supplementary information.
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Travis, A.R., Liau, V.A., Agrawal, A.C. et al. Small gold nanoparticles presenting linear and looped Cilengitide analogues as radiosensitizers of cells expressing ανβ3 integrin. J Nanopart Res 19, 361 (2017). https://doi.org/10.1007/s11051-017-4041-1
- Secondary structure
- Lung cancer