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

Abstract

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.

Keywords: EMT sensor; Mitochondria; Multi-stage responsive; Peptide recognition; Receptor induced self-assembly.