Labeling Monomeric Insulin with Renal-Clearable Luminescent Gold Nanoparticles

In the native physiological environment, inorganic nanoparticles (NPs) often induce nonspecific protein adsorption, which could significantly alter the function of the proteins they labeled. As a result, small fluorescent dyes are still widely used in the imaging of proteins in animals due to their minimal interference with protein function. Here, we used monomeric insulin as a model and compared its bioactivity before and after labeling with renal-clearable near-infrared-emitting gold NPs. These NPs were chosen because they have high resistance to serum protein adsorption and low nonspecific accumulation. We have found that a 1:1 insulin-NP ratio can be achieved, where the insulin-NPs show minimal serum protein binding with fully retained bioactivity comparable to that of unlabeled insulin. These results show a proof of concept that renal-clearable NPs can behave like small molecules in protein labeling without changing the individual protein's function, laying down a foundation for in vivo tracking of proteins with multimodality imaging techniques.