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Enabling AIEgens close assembly in tumor-overexpressed protein cluster for boosted image-guided cancer surgery
Science China Chemistry ( IF 9.6 ) Pub Date : 2020-10-20 , DOI: 10.1007/s11426-020-9829-x
Junxiao Gao , Jun Li , Daohe Wei , Han Yang , Yue Duan , Yue Zhang , Xiaoqun Gong , Hanjie Wang , Dan Ding , Xiaoli Wu , Jin Chang

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.



中文翻译:

使AIEgens在肿瘤过度表达的蛋白簇中紧密组装以增强图像引导的癌症手术

迫切需要开发能够实现具有极高的肿瘤与正常组织(T / NT)之比的精确荧光图像引导的癌症手术(FIGCS)的高效荧光探针。本文中,我们报告了一种基于聚集诱导发射(AIE)活性,基于肽的荧光开启探针MPA-Ph-R-FFGYSAYPDSVPMPMMS(简称MPA-Ph-R-FFGYSA)的设计和合成,包括:一个新的近红外发射AIE发光源(AIEgen)MPA-Ph-R,一个自组装肽序列“ FFG”和一个“活性”靶向肽YSAYPDSVPMMS,可以选择性地与许多癌症中过表达的EphA2蛋白簇结合。与不含“ FFG”的对照探针MPA-Ph-R-YSA相比,MPA-Ph-R-FFGYSA在细胞和体内均显示出更高的荧光亮度和灵敏度对EphA2簇检测/成像的研究,因为“ FFG”有利于AIEgen在EphA2簇中更紧密地组装,从而导致更有效地限制AIEgen的分子内运动。体内研究表明,MPA-Ph-R-FFGYSA是一种安全的生物探针,在FIGCS中具有优异的性能,静脉注射入腹膜癌的小鼠中T / NT值约为13.4,相当高。该研究提供了利用紧密组装的肿瘤微环境反应性AIE探针增强FIGCS的新策略。

更新日期:2020-10-30
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