Biomimetic Sensing System for Tracing Pb²⁺ Distribution in Living Cells Based on the Metal–Peptide Supramolecular Assembly

Abstract

Metal–peptide interactions provide plentiful resource and design principles for developing functional biomaterials and smart sensors. Pb2+, as a borderline metal ion, has versatile coordination modes. The interference from competing metal ions and endogenous chelating species greatly challenges Pb2+ analysis, especially in complicated living biosystems. Herein, a biomimetic peptide-based fluorescent sensor GSSH-2TPE was developed, starting from the structure of a naturally occurring peptide glutathione. Lewis acid–base theory was employed to guide the molecular design and tune the affinity and selectivity of the targeting performance. The integration of peptide recognition and aggregation-induced emission effect provides desirable sensing features, including specific turn-on response to Pb2+ over 18 different metal ions, rapid binding, and signal output, as well as high sensitivity with a detection limit of 1.5 nM. Mechanism investigation demonstrated the balance between the chelating groups, and the molecular configuration of the sensor contributes to the high selectivity toward Pb2+ complexation. The ion-induced supramolecular assembly lights up the bright fluorescence. The ability to image Pb2+ in living cells was exhibited with minimal interference from endogenous biothiols, no background fluorescence, and good biocompatibility. With good cell permeability, GSSH-2TPE can monitor changes in Pb2+ levels and biodistribution and thus predict possible damage pathways. Such metal–peptide interaction-based sensing systems offer tailorable platforms for designing bioanalytical tools and show great potential for studying the cell biology of metal ions in living biosystems.

Peptide‐Engineered Fluorescent Nanomaterials: Structure Design, Function Tailoring, and Biomedical Applications

“…The conjugated peptide chains offer improved biocompatibility for those fluorescent nanomaterials, endowing them as promising biosensors toward in vivo detection of cells, proteins, and enzymes. [ 183 ] In addition, fluorescent nanomaterials assembled with design tailored peptide sequences have been verified to promote both selectivity and sensitivity of biosensors. [ 184 ] Recently, double‐ligands stabilized fluorescent AuNCs/graphene nanocomplex was designed as a fluorescent biosensor for the detection of metalloproteinase‐9 bioassay from human breast adenocarcinoma MCF‐7 cells.…”

Self‐Assembled Peptide‐Based Nanoprobes for Disease Theranostics and Disease‐Related Molecular Imaging

“…Moreover, the peptide‐based nanoprobes responsive to other substrates such as metal ions, cysteine and protein thiols were explored as well. For example, Zhao and co‐workers developed a biomimetic peptide‐based fluorescent sensor GSSH‐2TPE (10) to image Pb 2+ in vitro and in living cells ( Figure A). The final product GSSH‐2TPE was obtained through the direct oxidation of GSH‐TPE.…”

Recent Advances in AIEgens for Metal Ion Biosensing and Bioimaging

“…By using the turn-on response of PSC1 towards Al 3+ , Fe 3+ , and Cr 3+ , cell imaging experiments with RAW 264.7 cells were performed. [103]. (Reproduced with permission from [102,103]).…”

“…Peptides with tailorable structures and rich coordination chemistry provide rich resource for designing recognition blocks. Huang and coworkers designed a Pb 2+ -specific sensor by mimicking the structure of GSH [103] (Figure 10b). Lewis acid-base theory was employed to guide the modulation of the selectivity of the probe.…”

“…After the oxidation of side groups, the probe GSSH-2TPE selectively recognized Pb 2+ with high affinity due to the matched coordination configuration and cavity size. The complex [103]. (Reproduced with permission from [102,103]).…”