Electrochemiluminescence resonance energy transfer immunosensing system based on PTC@UIO-66-NH₂ metal–organic framework and MnO₂ nanosheets for sensitive detection of vascular endothelial growth factor

Introduction: Vascular endothelial growth factor (VEGF) is acknowledged as a crucial biomarker for tumor angiogenesis, playing a significant role in the progression, development, and metastasis of tumors. Therefore, developing an ultra-sensitive detection method for VEGF is vital for early cancer prevention and surveillance of disease status.

Methods: In this research, we constructed a sandwich-style quenching electrochemiluminescence (ECL) immunosensor by employing the mechanism of electrochemiluminescence resonance energy transfer (ECL-RET), aiming for highly sensitive identification of VEGF₁₆₅.

Results: The PTC@UIO-66-NH₂ complex was prepared by integrating the organic luminescent probe, derived from the ammonolysis of Perylene-3,4,9,10-tetracarboxylic dianhydride (PTC), into the UIO-66-NH₂ metal–organic framework. This complex was subsequently modified on the surface of a polished carbon electrode to serve as an ECL substrate. The VEGF antibody was then conjugated to this substrate via an amide reaction. Meanwhile, bovine serum albumin-functionalized MnO₂ nanosheets (BSA-MnO₂), which were linked to VEGF₁₆₅ aptamers, functioned as the ECL acceptor. Upon selective recognition and binding to VEGF₁₆₅, ECL-RET occurred between the PTC@UIO-66-NH₂ (ECL donor) and BSA-MnO₂ (ECL acceptor), leading to a significant reduction in the ECL signal, which could be readily captured by the instrument. Additionally, the intensity of the ECL response diminished as the concentration of VEGF₁₆₅ increased. Under optimal experimental conditions, the ECL immunosensor exhibited a linear detection range spanning from 5 pg/mL to 50 ng/mL, with a minimum detectable limit of 3.5 pg/mL, which underscores its exceptional sensitivity. Furthermore, the ECL-RET immunoassay was subjected to rigorous validation procedures to confirm its specificity and stability.

Conclusions: In a nutshell, our ECL immunosensor presents a novel method for the early identification of VEGF in human serum, offering a fresh approach for timely detection. Furthermore, this technology depicts its potential to function as a flexible and promising platform, capable of detecting other circulating tumor biomarkers.