Ultrahighly Efficient and Stable Fluorescent Gold Nanoclusters Coated with Screened Peptides of Unique Sequences for Effective Protein and Serum Discrimination

Abstract

Gold nanoclusters (Au NCs) coated with various peptides have been widely used as fluorescent probes, and nowadays the most commonly used are cysteine (C) and tyrosine (Y) based ones. Herein, we report the preparation and clinical application of highly efficient and stable fluorescent Au NCs protected by screened peptides with a specific amino acid sequence Cys-Met-Met-Met-Met-Met (CMMMMM). Compared with traditional C, Y based peptide (CYYYYY) protected Au NCs, the fluorescence intensity of the CMMMMM-Au NCs increased by 230%, and the photobleaching resistance or stability of the CMMMMM-Au NCs increased by about 300% (after continuous ultraviolet irradiation for 60 min, the fluorescence of the CMMMMM-Au NCs remained more than 90% of their initial intensity, while the CYYYYY-Au NCs remained less than 30%). Assaying arrays based on CMMMMM protected Au NCs with different positive or negative charges as sensing receptors were developed through regulating different pH values, and multivariate analysis on the patterns obtained by these arrays allowed effective identification of not only ten proteins separately but also complex protein mixtures with subtly diverse compositions. The docking simulation and isothermal titration confirmed that target proteins interacted with CMMMMM-Au NCs mainly through electrostatic interactions and partly hydrophobic interactions, which affected the binding energy and fluorescence lifetime of CMMMMM-Au NCs, resulting in the unique fingerprint-like recognition patterns. Furthermore, serums from breast cancer, severe osteoarthritis, and rectal cancer patients can be effectively identified with healthy people using this CMMMMM-Au NCs based sensor array.

Biomolecular interactions of ultrasmall metallic nanoparticles and nanoclusters

“…For example, these particles can be uniformly coated with a wide array of charged ligands 54 (see Fig. 1b for examples), non-functional peptides, 55 carbohydrates, 56 DNA, 57 or combinations of different moieties, e.g., charged/hydrophobic or zwitterionic/hydrophobic, 58,59 to generate more complex surface architectures. Charged usGNPs, in particular, can bind with high affinity to regions of opposite charge on protein surfaces.…”

Array-Based Discriminative Optical Biosensors for Identifying Multiple Proteins in Aqueous Solution and Biofluids

“…Furthermore, this sensor array was able to identify complex protein mixtures and HSA at different concentrations in water and urine. Subsequently, Xu et al ( 2019 ) synthesized a type of Au NCs coated with screened peptides of specific sequences, and developed a sensor array with different positive or negative charges through adjusting pH values (pH 1.5, 3.5, 6.0, 10.0, and 11.5). This sensor array could identify not only 10 proteins, but also protein mixtures with diverse components.…”

Regulation of Surface Structure of [Au9Ag12(SAdm)4(Dppm)6Cl6](SbF6)3 Nanocluster via Alloying

“…Atomically precise core-shell nanoclusters have become a promising material in catalysis, biomedicine, and chemical sensing due to the unique quantum confinement effect resulting in optical properties ( Jin et al, 2016 ; Yao et al, 2018 ; Xu et al, 2019 ; Jin R. et al, 2021 ; Sun et al, 2021 ; Zheng et al, 2021 ). The studies on correlation between the properties and structures of cluster compounds based on the determined crystal structures show that the core and shell structures have different effects on the performance of the cluster compounds, and modifications on the core and shell structures may induce variations on clusters properties ( AbdulHalim et al, 2014 ; Chakraborty and Pradeep, 2017 ; Khatun et al, 2018 ; Yan et al, 2018 ; Jin Y. et al, 2021 ).…”