Epitope‐Imprinted Polymer Nanoparticles Enable Selective Recognition of Filamentous Vimentin for Tumor Imaging In Vivo

ABSTRACT Vimentin is a cytoskeletal protein upregulated during epithelial‐mesenchymal transition that can also be aberrantly displayed on the surface of multiple tumor cell types, making it a promising target for tumor imaging. Here, we develop epitope‐imprinted polymer nanoparticles (nanoMIPs) for vimentin recognition through a two‐step strategy comprising screening a library of non‐imprinted nanoparticles to identify a lead formulation, followed by peptide‐directed molecular imprinting. The resulting nanoMIPs exhibited enhanced apparent affinity for vimentin, with picomolar‐range K D values, although these values represent model‐dependent ensemble apparent affinities that may include contributions from multiple nanoparticle‐ligand contacts and local rebinding rather than intrinsic monovalent affinities. The nanoMIPs preferentially bound cancer cells presenting cell‐surface vimentin in vitro. The enhanced target binding and reduced off‐target binding were consistent with an imprinting‐associated improvement in molecular discrimination, although nonspecific physicochemical interactions were not completely eliminated. These findings extend epitope‐guided nanoMIP design to structurally dynamic, cell surface‐associated cytoskeletal targets, and support the development of synthetic receptors for tumor imaging. In vivo, the optimized nanoMIPs produced a tumor‐associated fluorescence signal approximately 1.44 times that of the matched non‐imprinted nanoparticles.