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.
Key Laboratory of Luminescence and Real-time Analytical Chemistry (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, No. 2 Tiansheng Road, Beibei, Chongqing 400715 (China).
Yan
Y
Zhang
Chunyue
C
Deng
Sha
S
Liu
Jin
J
Wu
Zhangbao
Z
Chen
Chong
C
Li
Weiyue
W
Lu
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D000939:Epitopes / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008819:Mice, Nude; D054802:Molecular Imprinting; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010778:Photochemotherapy; D017433:Protein Structure, Secondary; D014183:Transplantation, Heterologous
D004337:Drug Carriers; D000939:Epitopes; D009842:Oligopeptides; C528066:methionyl-leucyl-prolyl-histidyl-histidyl-glycyl-alanine; D001030:Apamin
conformational epitopes; drug delivery; imprinting; photodynamic therapy; tumor targeting