Enabling AIEgens close assembly in tumor-overexpressed protein cluster for boosted image-guided cancer surgery  

作　　者：Junxiao Gao Jun Li Daohe Wei Han Yang Yue Duan Yue Zhang Xiaoqun Gong Hanjie Wang Dan Ding Xiaoli Wu Jin Chang 

机构地区：[1]School of Life Sciences,Tianjin University,Tianjin 300072,China [2]Key Laboratory of Bioactive Materials,Ministry of Education,College of Life Sciences,Nankai University,Tianjin 300071,China

出　　处：《Science China Chemistry》2020年第11期1694-1702,共9页中国科学（化学英文版）

基　　金：This work was supported by the Tianjin Technical Expert Project(19JCTPJC41200);the National Natural Science Foundation of China(51873150,31770974);the National Key Research and Development Program of China(Intergovernmental Cooperation Project,2017YFE0132200).

摘　　要：Development of efficient fluorescent probes that can realize precise fluorescence image-guided cancer surgery(FIGCS)with extremely high tumor-to-normal tissue(T/NT)ratio is urgently desirable.Herein,we report the design and synthesis of an aggregation-induced emission(AIE)-active,peptide-based fluorescence turn-on probe MPA-Ph-R-FFGYSAYPDSVPMMS(MPA-Ph-R-FFGYSA for short),which consists of a new near-infrared emissive AIE luminogen(AIEgen)MPA-Ph-R,a self-assembling peptide sequence“FFG”,and an“active”targeting peptide YSAYPDSVPMMS that can selectively bind to EphA2 protein cluster overexpressed in many cancers.As compared to the control probe MPA-Ph-R-YSA without“FFG”,MPA-Ph-R-FFGYSA exhibits much higher fluorescent brightness and sensitivity in both cellular and in vivo studies on EphA2 cluster detection/imaging,as“FFG”is beneficial to closer assembly of AIEgens in EphA2 cluster,leading to more effective restriction of the intramolecular motion of AIEgen.In vivo studies demonstrate that MPA-Ph-R-FFGYSA is a safe bioprobe and gives excellent performance in FIGCS with a rather high T/NT ratio of^13.4 upon intravenous administration into peritoneal carcinomatosis-bearing mice.This study provides a new strategy of utilizing the close assembly of tumor microenvironment-responsive AIE probes for boost FIGCS.

关 键 词：aggregation-induced emission luminogen fluorescent probe self-assembling peptide fluorescence image-guided cancer surgery tumor-to-normal tissue ratio 

分 类 号：R730.56[医药卫生—肿瘤]