Quantification of Poly(ethylene glycol) Crowding on Nanodiamonds toward Quantum Biosensor for Improved Prevention Effects on Protein Adsorption and Lung Accumulation.

Nanometer-sized diamonds (NDs) containing nitrogen vacancy centers have garnered significant attention as potential quantum sensors for reading various types of physicochemical information in vitro and in vivo. However, NDs intrinsically aggregate when placed in biological environments, hampering their sensing capacities. To address this issue, the grafting of hydrophilic polymers onto the surface of NDs has been demonstrated considering their excellent ability to prevent protein adsorption. To this end, crowding of the grafted chains plays a crucial role because it is directly associated with the antiadsorption effect of proteins; however, its quantitative evaluation has not been reported previously. In this study, we graft poly(ethylene glycol) (PEG) with various molecular weights onto NDs, determine their crowding using a gas adsorption technique, and disclose the cross-correlation between the pH in the grafting reaction, crowding density, molecular weight, and the prevention effect on protein adsorption. PEG-grafted NDs exhibit a pronounced effect on the prevention of lung accumulation after intravenous injection in mice. PEG crowding was compared to that calculated by using a diameter determined by dynamic light scattering (DLS) assuming a sphere.