Charged Gold Nanoparticles with Essentially Zero Serum Protein Adsorption in Undiluted Fetal Bovine Serum

The adsorption of even a single serum protein molecule on a gold nanosphere used in biomedical imaging may increase the size too much for renal clearance. In this work, we designed charged ∼5 nm Au nanospheres coated with binary mixed-charge ligand monolayers that do not change in size upon incubation in pure fetal bovine serum (FBS). This lack of protein adsorption was unexpected in view of the fact that the Au surface was moderately charged. The mixed-charge monolayers were composed of anionic citrate ligands modified by place exchange with naturally occurring amino acids: either cationic lysine or zwitterionic cysteine ligands. The zwitterionic tips of either the lysine or cysteine ligands interact weakly with the proteins and furthermore increase the distance between the “buried” charges closer to the Au surface and the interacting sites on the protein surface. The ∼5 nm nanospheres were assembled into ∼20 nm diameter nanoclusters with strong near-IR absorbance (of interest in biomedical imaging and therapy) with a biodegradable polymer, PLA(1k)-b-PEG(10k)-b-PLA(1k). Upon biodegradation of the polymer in acidic solution, the nanoclusters dissociated into primary ∼5 nm Au nanospheres, which also did not adsorb any detectable serum protein in undiluted FBS.