Sequential Antifouling Surface for Efficient Modulation of the Nanoparticle–Cell Interactions in Protein‐Rich Environments

Abstract

AbstractModulating the nanoparticle (NP)–cell interactions in protein‐rich environments is of increasing significance to nanomedicine. One major challenge is that the synthetic identity (such as targeting) of NPs endowed for this purpose can be adversely altered by opsonization processes. The formed protein corona on NPs can cause fast clearance of NPs by macrophages and reduced cancer cell uptake. The transformable NPs, which are grafted with a cleavable antifouling surface to achieve inactive‐active targeting form conversion, offer great promise to efficiently modulate NP–cell interactions. However, most of the transformable NPs lack a sustainable protection mechanism to avoid the influence of the protein corona during the post‐transformation period, leading to the re‐opsonization on NPs. Here, the authors design a smart transformable nanosystem with a photo‐triggered zwitterion‐induced sequential antifouling surface to efficiently reduce protein adsorption on NPs and modulate the NP–cell interactions in protein‐rich environments. The authors demonstrate that the primary PEGylated antifouling surface could protect the NPs against uptake by macrophages. Furthermore, the photo‐induced secondary zwitterionic antifouling surface is shown to preserve the targeting capacity of biotin‐modified NPs during the post‐transformation period in protein‐rich environments. In contrast, the biotin‐conjugated NPs without antifouling surfaces almost lost the targeting specificity in protein‐rich environment.