Probing the Cellular Uptake of DNA Functionalized Gold Nanoparticles

Abstract

Gold nanoparticles conjugated to short sensing strands of DNA have been successfully applied to therapeutic silencing and intracellular detection of disease-associated mRNAs. These biomedical applications are possible because DNA functionalized gold nanoparticles (DNA-AuNPs) are efficiently internalized by cells, without requiring transfection agents. The 3D structure of the assembled DNA monolayer promotes binding of the nanoparticles to scavenger receptor proteins on the cell surface, which then mediate the endocytic translocation of the DNA-AuNPs into the cell. Although a mechanism of cellular uptake has been reported, many questions remain about the biological and physicochemical properties that control DNA-AuNP internalization. DNA-AuNPs accumulated at the membrane of protein-free giant unilamellar vesicles, but not inside the vesicle, suggesting that the nanoparticles are capable of interacting with phospholipids, but proteins are required for translocation of the membrane. A systematic investigation of the physicochemical properties of DNA-AuNPs revealed that the size determines the degree of nanoparticle accumulation in cells. Finally, DNA-AuNPs were accumulated by cells originating from different organisms, suggesting that the mechanism of DNA-AuNP binding uptake may be conserved across species.