Self-Assembly of Amphiphilic Peptides for Recognizing High Furin-Expressing Cancer Cells

Abstract

Self-assembled nanostructures of amphiphilic peptides have a wide range of applications in bioimaging and delivery systems. In this study, we design and synthesize a biocompatible amphiphilic peptide (C-3) consisting of an RVRRFFF sequence and a nitrobenzoxadiazole fluorophore that can self-assemble into stable micelles for specifically detecting furin, a kind of proprotein convertase with promoting tumor progression. The self-assembly of C-3 with a β-sheet nanostructure is capable of a rapid and specific response to furin in only 5 min in aqueous solution because of the existence of the RVRR motif in the C-3 molecule. The C-3 nanostructures thus can selectively distinguish high furin-expressing cancer cells, like MDA-MB-231 cells, a kind of human breast cancer cells, from normal cells. Furthermore, the C-3 self-assembly can stay in living cells for a long time and are capable of durable detection of intracellular furin, being good for tracer analysis. To our knowledge, this is the first example of self-assembly of a soluble amphiphilic peptide that can selectively detect furin in high furin-expressing live cells.

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

“…Li et al. 291 constructed an amphiphilic peptide, an Arg-Val-Arg-Arg-Phe-Phe-Phe-NBD (a nitrobenzoxadiazole) sequence. Among which, NBD was a hydrophobic environment-enhanced fluorescent chromophore.…”

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

“…Self-assembled peptide-based micelles can also be used for disease diagnosis, in particular in cancer. Self-assembled micelles based on C-3, an amphiphilic RVRRFFF peptide coupled to a nitrobenzoxadiazole fluorophore (NBD) were developed for recognizing cancer cells with high furin expression since RVRR is a cleavage site for furin [44]. When taken up by living cells, C-3 micelles allowed the successful detection of furin by the dissociation of micelles accompanied by an increase in fluorescence.…”

Biomaterials based on noncovalent interactions of small molecules

“…The tunability and biocompatibility of EISA allow aberrant levels of enzymes to catalyze the accumulation of imaging agents in situ to obtain accurate and precise imaging. Pioneered by Liang et al (2010[ 58 ]), furin-guided CBT condensation initiates self-assembly process to form nanoparticles with dense imaging agents, facilitating MicroPET imaging (Wang et al, 2019[ 78 ]; Liu et al, 2015[ 62 ]), fluorescence (Li et al, 2019[ 55 ]), and phosphorescence imaging (Li et al, 2018[ 51 ]) in different cases. As reported by Liang et al, ALP-instructed self-assembly generates nanofibers for enhanced CT (Zheng et al, 2016[ 119 ]) and MRI (Dong et al, 2017[ 14 ]).…”