Pillar[6]arene@AuNPs Functionalized N-CQDs@Co₃O₄ Hybrid Composite for Ultrasensitive Electrochemical Detection of Human Epididymis Protein 4

Abstract

Hydroxylatopillar[6]arene (HP6) has been used as a stable ligand for the synthesis of gold nanoparticles (AuNPs). HP6 with excellent molecular recognition capability will securely capture the electron transfer medium thionin (Thi). Compared with other electroactive molecular capture methods (physical adsorption, etc.), the formation of an HP6⊃Thi complex can effectively inhibit the leakage of Thi and significantly increase the loading of Thi. HP6@Au was prepared in an aqueous solution with OH − at room temperature through an oxidation−reduction reaction between HP6 and AuCl 4 − , without the need for conventional harsh reducing agents. X-ray photoelectron spectroscopy and Fourier transform infrared studies have shown that the −OH groups in HP6 are oxidized to −COOH groups, and Au 3+ in AuCl 4− is reduced to Au 0 , leading to nucleation and production of AuNPs. The formation of HP6@Au strengthens the electron transfer rate, increases surface area, and captures a large number of primary antibodies (Ab1). Besides, the surface of N-doped carbon quantum dots and cobalt oxide (N-CQDs@Co 3 O 4 ) can be used for the deposition of HP6@ Au by π−π interaction to form a green highly conductive nanocomposite. An electrochemical immunosensor with significant stability was constructed based on HP6@Au/N-CQDs@Co 3 O 4 , and it was used for the effective detection of human epididymis protein 4 (HE4). The detection limit of the proposed immunosensor platform is 1.5 pg mL −1 , and it provides a wide linear range from 0.002 to 20 ng mL −1 under optimal conditions. The analysis results of HE4 in human serum are satisfactory and have broad application prospects in clinical monitoring.

Multifunctional Pillar[n]arene-Based Smart Nanomaterials

“…Moving toward green synthesis of gold nanoparticles, hydroxylatopillar[−]­arene derivatives ( 1 – 3 , Scheme ) have been reported as both reducing and stabilizing agents of gold nanoparticles (AuNPs). In this alkaline process, sodium hydroxide assists the formation of Au­(OH) 4 – complex, promoting the redox reaction with the hydroxy groups of 1 – 3 , resulting in the synthesis of 1 – 3 @AuNP with an average size of 5–6 nm and the oxidation of 1 – 3 to the carboxylic form. − More recently, a leaning pillar[6]­arene, containing eight carboxylate groups 4 (Scheme ), reduced and stabilized the hydrothermal synthesis of AuNP. However, due to the lower quantity of stabilizing ligands, bigger nanoparticles of ∼11 nm were obtained …”

“…In addition to metals, carbon-based nanostructures have also been functionalized with PAs via two methods. The first one consists of loading PA ( 5 , 10 , and 12 ; Scheme ) or PA–NP ( 1 – 3 ) into a nanomaterial, typically in the form of nanosheets, by mixing aqueous dispersions at room temperature and recovering the modified nanocomposite by centrifugation. ,,− In the second method, the PA-modified nanomaterial is synthesized in a one-step hydrothermal synthesis ( 11 ; Scheme ). In both cases, the PAs are anchored on the surface of the nanomaterial by π–π interactions, and PA–NP can be further stabilized via coordination bonds of the metallic NP with the nanomaterial.…”

“…To further enhance the electrochemical detection of HE4 (an ovarian biomarker), a composite material ( 3 @AuNP-Co 3 O 4 @N-CQDs) with Co 3 O 4 @N-CQDs was prepared, which was driven by π–π interactions between 3 @AuNP and the quantum dots (Figure ). Since AuNP and Co 3 O 4 @N-CQDs improve electron transfer and the absorption of ferricyanide ions, and the presence of 3 provides a greater recognition system, a lower limit of detection and enhanced selectivity were achieved …”

“…Schematic illustration of the electrochemical immunosensor 3 @AuNP–Co 3 O 4 @N-CQDs preparation for ovarian biomarker detection. Reprinted in part with permission from ref . Copyright 2020 American Chemical Society.…”

“…Since AuNP and Co 3 O 4 @N-CQDs improve electron transfer and the absorption of ferricyanide ions, and the presence of 3 provides a greater recognition system, a lower limit of detection and enhanced selectivity were achieved. 18 Similarly, Tan et al reported a p-dinitrobenzene (p-DNB) sensor consisting of a hybrid nanomaterial (1@AuNP−11@ MoS 2 ). MoS 2 was chosen given its high electrocatalytic activity and conductivity, and was modified with cationic pillar [5]arene 11, improving its water dispersibility and stability for up to 3 months.…”