Abstract
Antifouling polymer brushes are widely used to inhibit the formation of protein corona on nanoparticles (NPs) and subsequent accumulation in the liver and spleen. Herein, we demonstrate a θ-solvent-mediated method for the preparation of gold nanoparticles with a high polyethylene glycol (PEG) grafting density. Reaching the θ-solvent by adding salt (e.g., Na2SO4) can significantly increase the grafting density of the PEG brush to 2.08 chains/nm2. The PEG polymer brush prepared in the θ-solvent possesses a double-shell structure consisting of a concentrated polymer brush (CPB) and a semidilute polymer brush (SDPB), denoted as NP@CPB@SDPB, while those prepared in a good solvent have only a SDPB shell, i.e., NP@SDPB. Compared to the NP@SDPB structure, the NP@CPB@SDPB structure decreases the liver accumulation from 34.0%ID/g to 23.1%ID/g, leading to an increase in tumor accumulation from 8.5%ID/g to 12.8%ID/g. This work provides new insights from the perspective of polymer physical chemistry into the improved stealth properties and delivery efficiency of NPs, which will accelerate the clinical translation of nanomedicine.
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