Tuning of ultrasmall gold nanoparticles surface properties affect their biological fate

Ultrasmall nanoparticles of 10 nm or less in size have been shown to have great potential in the biomedical field due to their high surface area and strong tissue penetration. Their easy functionalization and unique behavior at the nanoscale, such as the reduced corona formation and lower liver retention allow them to be a potential tool for precision targeting. In this study, PEGylated ultrasmall gold nanoparticles (GNPs) with a 4 nm core size are developed. They are functionalized with the cyclic RGD (cRGD) targeting peptide, which provides high binding affinity toward αVβ3 integrin receptor, often overexpressed in solid tumors. Further evidence is presented that cRGD functionalized GNPs partially escape lysosomes while penetrating deeper into the liver parenchyma. These particles provide a potential future strategy for specific αVβ3 integrin targeting.