A dual-aptamer-based biosensor for specific detection of breast cancer biomarker HER2 via flower-like nanozymes and DNA nanostructures

Abstract

Developing highly sensitive and selective detection strategies for biomarkers is beneficial for fundamental research and disease diagnosis. Herein, we constructed a sandwich-type electrochemical aptasensor to detect the breast cancer cell biomarker Human Epidermal Growth Factor Receptor 2 (HER2). The aptasensor was a combination of tetrahedral DNA nanostructures (TDNs)–aptamer as recognition probes and flower-like nanozymes/horseradish peroxidase (HRP) as signal nanoprobes. In the process of assembling the biosensor, the TDN–aptamer 1 as a bio-recognition element was immobilized on the gold electrode (GE) surface for capturing the biomarker HER2. The nanozyme Mn₃O₄ was decorated by Pd@Pt nanozymes which were linked by the aptamer 2 and natural enzyme HRP. The designed Mn₃O₄/Pd@Pt/HRP nanoprobe (nanoprobe 1) was used to amplify the biosensor signal via catalyzing the oxidation of hydroquinone (HQ) with hydrogen peroxide (H₂O₂). After binding HER2, an aptamer–protein–nanoprobe sandwich system was fabricated on the GE surface. Lastly, a Pd@Pt/HRP/complementary DNA (cDNA) nanoprobe (nanoprobe 2) was added on the surface of nanoprobe 1 through DNA hybridization of aptamer 2 and cDNA to form a dendritic DNA nanostructure to further amplify the signal significantly. The results indicate that the aptasensor shows a broad linear response from 0.1 to 100.0 ng mL⁻¹ and the low detection limit is 0.08 ng mL⁻¹. The designed approach holds great potential for the construction of various aptasensors for the effective and convenient detection of different biomarkers.