Ultrasmall nanoparticles provide us with essential alternatives for designing more efficient nanocarriers for drug delivery. However, the fast clearance of ultrasmall nanoparticles limits their application to some extent. One of the most frequently used compound to slow the clearance of nanocarriers and nanodrugs is PEG, which is also approved by FDA. Nonetheless, few reports explored the effect of the PEGylation of ultrasmall nanoparticles on their behavior in vivo. Herein, we investigated the impact of different PEG grafting level of 2 nm core sized gold nanoparticles on their biological behavior in tumor-bearing mice. The results indicate that partial (∼50%) surface PEGylation could prolong the blood circulation and increase the tumor accumulation of ultrasmall nanoparticles to a maximum extent, which guide us to build more profitable small-sized nanocarriers for drug delivery.
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