Multi-stage responsive peptide nanosensor: Anchoring EMT and mitochondria with enhanced fluorescence and boosting tumor apoptosis

• Published in: Biosensors & bioelectronics 2021-07, Vol.184, p.113235-113235, Article 113235
• Main Authors: Tian, Yuwei, Zhang, Limin, Liu, Fangjie, Wang, Minxuan, Li, Lingyun, Guo, Mingmei, Xu, Hangyu, Yu, Zhiying, Wang, Weizhi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biosensing Techniques; Cell Line, Tumor; Cell Movement; EMT sensor; Epithelial-Mesenchymal Transition; Mice; Mice, Nude; Mitochondria; Multi-stage responsive; Peptide recognition; Peptides; Receptor induced self-assembly
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2021.113235

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 NDRP 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. NDRP 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. •NDRP was obtained from a rational designed high-content screening through which we can get a new peptide sequence with affinity, specificity, self-assembly potential, and receptor-triggered ability simultaneously.•For the sequence, we set some elements such as ‘alternate residues’, ‘β-sheet contributor’ and ‘Pro switching’, which is preferred to response the EMT marker and emit enhanced fluorescent signal.•The self-assembly peptide could initiate aggregation in the tumor sites and transform into activated nanofibrils through ligand-receptor interactions. Also, exposed binding sites would recruit additional nanofibers specifically in mesenchymal tumor cells.•NDRP could specifically target the mitochondria of mesenchymal tumor as well as evidently damage mitochondria, thus providing a promising therapeutic strategy for tumors.