Correlating Ligand Density with Cellular Uptake of Gold Nanorods Revealed by X-ray Reflectivity

Ligands can endow unique physicochemical properties of nanomaterials and also mediate biological effects of nanomaterials. It is unclear whether the ligand density affects cytotoxicity and uptake. Herein, we studied the interaction between poly(diallyldimethylammonium chloride)-coated gold nanorods (PDC-Au) and endothelial cells, in which these PDC-Au possessed a series of ligand densities after the storage for different days. We found that PDC-Au with higher density of ligand did not induce obvious cytotoxicity and damage membrane, but more of them were internalized by cells than those with lower ligand density. A powerfully quantitative method, liquid surface X-ray reflectivity, demonstrated that more gold nanorods can be adsorbed on the phospholipid monolayer for PDC-Au with higher ligand density, which directly correlated to the results of cell uptake. The study emphasized the importance of surface ligand density in the evaluation of biological effects of nanomaterials and suggested a cautious consideration in the ligand stability during the design of nanomaterials and their application. Moreover, according to X-ray reflectivity, interfacial analysis is helpful for the study about the interaction between biological membranes and multiple nanomaterials in future, which provides quantitative and structural information.