Tian Yuwei, Zhang Limin, Liu Fangjie, Wang Minxuan, Li Lingyun, Guo Mingmei, Xu Hangyu, Yu Zhiying, Wang Weizhi
Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, PR China.
National Center for Nanoscience and Technology, Beijing 100190, PR China.
Biosens Bioelectron. 2021 Jul 15;184:113235. doi: 10.1016/j.bios.2021.113235. Epub 2021 Apr 19.
Epithelial-mesenchymal transition (EMT) is closely related to tumor metastasis and invasion. Thereinto, mesenchymal tumor mitochondria are the critical target for tumor inhibition. Therefore, real-time in vivo monitoring of EMT as well as inhibiting mesenchymal tumor mitochondria is of great diagnosis and therapy significance. Herein, we construct a multi-stage recognition and morphological transformable self-assembly-peptide nano biosensor DRP which can response the EMT marker and specifically damage the mesenchymal tumor cell in vivo. This nano-molar-affinity sensor is designed and screened with sensitive peptides containing a molecular switching which could be specifically triggered by the receptor to achieve the vesicle-to-fibril transformation in living system with enhanced fluorescent signal. DRP nanosensor could target the tumor lesion in circulatory system, recognize mesenchymal tumor marker DDR2 (Discoidin domain receptor 2) in cellular level and specifically achieve mitochondria in subcellular level as well as damaged mitochondria which could be applied as a in vivo theranostic platform.
上皮-间质转化（EMT）与肿瘤转移和侵袭密切相关。其中，间充质肿瘤线粒体是肿瘤抑制的关键靶点。因此，对EMT进行实时体内监测以及抑制间充质肿瘤线粒体具有重要的诊断和治疗意义。在此，我们构建了一种多阶段识别和形态可转化的自组装肽纳米生物传感器DRP，它可以响应EMT标志物并在体内特异性损伤间充质肿瘤细胞。这种纳摩尔亲和力传感器是用含有分子开关的敏感肽设计和筛选的，该分子开关可由受体特异性触发，以在具有增强荧光信号的活体系统中实现囊泡到纤维的转变。DRP纳米传感器可以靶向循环系统中的肿瘤病变，在细胞水平识别间充质肿瘤标志物DDR2（盘状结构域受体2），并在亚细胞水平特异性地作用于线粒体以及损伤线粒体，可作为一种体内诊疗平台。
