Peptide-Induced AIEgen Self-Assembly: A New Strategy to Realize Highly Sensitive Fluorescent Light-Up Probes

Abstract

Fluorescent light-up probes with aggregation-induced emission (AIE) characteristics have recently attracted great research interest due to their intelligent fluorescence activation mechanism and excellent photobleaching resistance. In this work, we report a new, simple, and generic strategy to design and prepare highly sensitive AIE fluorescent light-up bioprobe through facile incorporation of a self-assembling peptide sequence GFFY between the recognition element and the AIE luminogen (AIEgen). After the bioprobes respond to the targets, the peptide GFFY is capable of inducing the ordered self-assembly of AIEgens, yielding close and tight intermolecular steric interactions to restrict the intramolecular motions of AIEgens for excellent signal output. Using two proof-of-concepts, we have demonstrated that self-assembling peptide-incorporating AIE light-up probes show much higher sensitivity in sensing the corresponding targets in both solutions and cancer cells as compared to those without GFFY induced self-assembly. Taking the probe TPE-GFFYK(DVEDEE-Ac), for example, a detection limit as low as 0.54 pM can be achieved for TPE-GFFYK(DVEDEE-Ac) in caspase-3 detection, which is much lower than that of TPE-K(DVED-Ac) (3.50 pM). This study may inspire new insights into the design of advanced fluorescent molecular probes.

Self‐Assembly of Aggregation‐Induced‐Emission Molecules

“…Peptides show a strong self‐assembly ability owing to the formation of inter‐ or intramolecular hydrogen bonds. AIEgens with a peptide sequence show satisfactory self‐assembly ability . For example, the peptide sequence GFFY capped with an aromatic group is able to self‐assemble into nanofibers .…”

Supramolecular biofunctional materials

“…In this case this probe could be used for imaging caspase-3. [323] Yang et al also designed and synthesized a far-red/near-infrared (FR/NIR) fluorescence light-up probe (DBT-2EEGWRESAI) by conjugating two peptides with same sequences (EEGWRESAI, tax-interacting protein-1 (TIP-1) specific binding ligands) to both sides of a fluorophore 4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole (DBT). DBT is an environment-sensitive dye—in aqueous solutions, the probe DBT-2EEGWRESAI is weakly fluorescent while it lighted up upon the specific binding with TIP-1 or polyprotein ULD-TIP-1 to form nanofiber network or spherical nano-complexes.…”

Biomacromolecule‐Functionalized AIEgens for Advanced Biomedical Studies

“…Thus, the peptide‐based AIEgen could be regarded as an optimal tool to real‐time monitor the biological process of caspase‐8 and caspase‐3, further screen out the anticancer drugs, and evaluate its therapeutic effects. Furthermore, Liu and co‐workers developed a simple and effective strategy of peptide‐induced AIEgen self‐assembly for detection of caspase‐3, as shown in Figure C. The TPE‐GFFYKDVEDEE‐Ac was designed with self‐assembly peptide GFFY crosslink to reporter TPE and peptide DVEDEE‐Ac.…”

“…C) The chemical conjugate structure of the peptide GFFYKDEVDEE‐functionalized TPE TPE‐GFFYKDVEDEE‐Ac and its self‐assembly strategy for the detection of caspase‐3. Adapted with permission . Copyright 2016, American Chemical Society.…”