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

• 来源期刊: 中国科学：化学（英文版）
• 年，卷（期）: 2020,（11）
• 所属期刊栏目: ARTICLES
• 页码范围: 1694-1702
• 页数: 9页
• 语种: 英文

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 selfassembling 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 microenvironmentresponsive AIE probes for boost FIGCS.