Nanoassembled Peptide Biosensors for Rapid Detection of Matrilysin Cancer Biomarker

Abstract

high translational values. [7][8][9] Commonly, organic fluorophore dyes and quantum dots (QDs) have been employed in order to modify peptides such as Escherichia coli for fluorescent imaging and biosensing. [10,11] Still, fluorescent dyes have several issues such as susceptibility to photobleaching and slender specificity for bioconjugation to particular reactive sites. [12,13] Most QDs, on the other hand, suffer from cytotoxicity for biomedical applications. [14][15][16] Carbon quantum dots (CDs), [17] a class of 0D carbon nanomaterials (1-10 nm) with unique optical properties, high photo stability, excellent biocompatibility, and facile preparation are promising substitutes to fluorescent dyes and QDs. [18,19] In addition, gold nanoparticles (AuNPs) have shown remarkable physical and optical properties in nanomedicine applications, specifically in the field of nanobiosensors. [20][21][22] The chemical and physical interactions between AuNPs and proteins or peptides have already been characterized with biophysical, [23] biochemical, [24] and computational methods, [25] which indicate the diversity of AuNPs as an ideal model material for developing new peptide/protein optical biosensors. So far, several studies have been conducted aiming at manipulating peptide self-nanoassembly into desired nanoarchitectures for sensing applications. [26][27][28][29][30][31] For instance, peptide-functionalized AuNPs with tunable, reversible, [32] and irreversible [33,34] aggregations were synthesized as nanobiosensors to detect phospholipases and proteolytic activities, respectively. Yet, it remains a challenge to fully engineer the nanoarchitecture of peptide and hybrid nanoparticles to respond to minuscule concentrations of target analytes (e.g., cancer biomarker) in a short amount of time.In the light of the necessity for rapid detection of cancerrelated protein biomarkers, we have engineered a sensitive and selective fluorescent, label-free protein detection platform hereafter referred to as the PACD (peptide-Au-carbon dots) nanoprobe (Sections S1-S7, Supporting Information). We based this class of hybrid nanobiosensing platform on a synthetic polypeptide aptamer sensitive to the target biomarker which is anchored to AuNPs from one end and semiconducting zero dimensional CDs from the other end with niche electro-optical properties (Figure 1a). The polypeptide, referred to as the bioreceptor interchangeably, belongs to a family of helix-loophelix polypeptides de novo (JR2EC). [35] The bioreceptors and the surface-functionalized CDs were assembled step-wise on the surface of AuNPs, forming a stable nanoprobe (Figure 1b). As the active component of the nanobiosensors, JR2ECEarly detection of cancer is likely to be one of the most effective means of reducing the cancer mortality rate. Hence, simple and ultra-quick methods for noninvasive detection of early-stage tumors are highly sought-after. In this study, a nanobiosensing platform with a rapid response time of nearly 30 s is introduced for the detection of matrilysin-the sal...

Functionalized Gold Nanoparticles: Synthesis, Properties and Biomedical Applications

“…Peptide sequences from this common multi-diagnostic platform can also be used for realtime monitoring of drugs and disease detection. [71] As an innovative kind of porous crystal nanostructures, covalent organic frames (COF) have excellent thermal stability, diverse structures, and adsorbability. Nevertheless, it is undeniable that the specificity of COF limits its application as a sensor.…”

“…As shown in Figure 29 Absolute Zeta-potential of AuNPs, PA, and nanoprobes (the measured values are negative). [71] Reprinted with permission from [71]. Copyright 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…d) The selectivity of PACD nanoprobes, comparing the photoluminescence intensity of MMP-7, MMP-9, and BSA. [71] Reprinted with permission from [71]. Copyright 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…In Figure 28(c), by comparing with the calibration curve, it is also found that the nanoscale biosensor has a stable correlation at different concentrations and has a repeatability of detection. Peptide sequences from this common multi‐diagnostic platform can also be used for real‐time monitoring of drugs and disease detection [71] …”

“…(g) High‐performance liquid chromatog‐raphy of the nanoprobe and its components involving in the self‐nanoassembly reaction. (h) Absolute Zeta‐potential of AuNPs, PA, and nanoprobes (the measured values are negative) [71] . Reprinted with permission from [71].…”