Active Targeting of Tumors through Conformational Epitope Imprinting

Inspired by the knowledge that most antibodies recognize a conformational epitope because of the epitope’s specific three‐dimensional shape rather than its linear structure, we combined scaffold‐based peptide design and surface molecular imprinting to fabricate a novel nanocarrier harboring stable binding sites that captures a membrane protein. In this study, a disulfide‐linked α‐helix‐containing peptide, apamin, was used to mimic the extracellular, structured N‐terminal part of the protein p32 and then serve as an imprinting template for generating a sub‐40 nm‐sized polymeric nanoparticle that potently binds to the target protein, recognizes p32‐positive tumor cells, and successfully mediates targeted photodynamic therapy in vivo. This could provide a promising alternative for currently used peptide‐modified nanocarriers and may have a broad impact on the development of polymeric nanoparticle‐based therapies for a wide range of human diseases. Magic bullet: A peptide served as an “indirect” targeting ligand to mediate active tumor‐targeted drug delivery. A disulfide‐linked α‐helix containing peptide, apamin, was used to mimic the extracellular, structured N‐terminal part of the protein p32. The combination with surface molecular imprinting produced a nanocarrier that recognizes p32‐positive tumors in vivo.