Abstract Due to non‐specific strong nano–bio interactions, it is difficult for nanocarriers with permanent rough surface to cross multiple biological barriers to realize efficient drug delivery. Herein, a camouflaged virus‐like‐nanocarrier with a transformable rough surface is reported, which is composed by an interior virus‐like mesoporous SiO2 nanoparticle with a rough surface (vSiO2) and an exterior acid‐responsive polymer. Under normal physiological pH condition, the spikes on vSiO2 are hidden by the polymer shell, and the non‐specific strong nano–bio interactions are effectively inhibited. While in the acidic tumor microenvironment, the nanocarrier sheds the polymer camouflage to re‐expose its rough surface. So, the retention ability and endocytosis efficiency of the nanocarrier are great improved. Owing to it's the dynamically variable rough surface, the rationally designed nanocarrier exhibits extended blood‐circulation‐time and enhanced tumor accumulation.
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