Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers

Early detection and intervention in diabetic retinopathy (DR) are key to its prevention and treatment. In this study, we propose a surface-enhanced Raman scattering (SERS) bifunctional detection platform based on nanoenzymes catalyzing the tetramethylbenzidine (TMB) reaction, which innovatively intr...

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Main Authors: Binbin Zeng, Xia Zong, Xinjue Dai, Lian Pan, Xiaowei Cao, Changhua Lu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2025.1623332/full
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author Binbin Zeng
Xia Zong
Xinjue Dai
Lian Pan
Xiaowei Cao
Changhua Lu
author_facet Binbin Zeng
Xia Zong
Xinjue Dai
Lian Pan
Xiaowei Cao
Changhua Lu
author_sort Binbin Zeng
collection DOAJ
description Early detection and intervention in diabetic retinopathy (DR) are key to its prevention and treatment. In this study, we propose a surface-enhanced Raman scattering (SERS) bifunctional detection platform based on nanoenzymes catalyzing the tetramethylbenzidine (TMB) reaction, which innovatively introduces an aptamer recognition competition strategy and achieves an ultrasensitive detection of DR associated biomarker (VEGF). The platform employs Au@Pd nanorods (Au@Pd NRs) modified with single-stranded DNA1 (ssDNA1) as nanoenzymatic probes. Arrays of Au trioctahedra (Au TOHs) with surface-modified double-stranded structures, including aptamer strands and single-stranded DNA2 (ssDNA2), were used as capture substrates. When the target protein is present in the solution to be tested, the aptamer specifically recognizes the target protein and detaches from the surface of the capture substrate, exposing ssDNA2 and being recognized and bound by ssDNA1, allowing a large number of nanoenzymatic probes to be bound to the capture substrate, and the assay platform thus possesses excellent POD activity and SERS performance, being able to catalyze the generation of TMB with a strong SERS signal oxTMB. The platform demonstrated high detection performance, completing the assay within 14 min, with a low limit of detection (LOD) of 0.11 pg/mL. It maintained robust clinical performance even in complex serum samples, and the results were consistent with ELISA. This work offers a framework for constructing nanoenzyme-SERS bifunctional detection systems and introduces a new approach for biomarker detection.
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spelling doaj-art-b5eea184ec284a3a8b1726e9aba553a02025-08-20T03:12:43ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-07-011310.3389/fbioe.2025.16233321623332Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkersBinbin Zeng0Xia Zong1Xinjue Dai2Lian Pan3Xiaowei Cao4Changhua Lu5Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Institute of Translational Medicine, Yangzhou University, Yangzhou, ChinaOphthalmology, The Affiliated Yixing Traditional Chinese Medicine Hospital of Yangzhou University, Wuxi, ChinaDepartment of Endocrinology, The Affiliated Yixing Traditional Chinese Medicine Hospital of Yangzhou University, Wuxi, ChinaDepartment of Pathology, The Affiliated Yixing Traditional Chinese Medicine Hospital of Yangzhou University, Wuxi, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Institute of Translational Medicine, Yangzhou University, Yangzhou, ChinaOphthalmology, The Affiliated Yixing Traditional Chinese Medicine Hospital of Yangzhou University, Wuxi, ChinaEarly detection and intervention in diabetic retinopathy (DR) are key to its prevention and treatment. In this study, we propose a surface-enhanced Raman scattering (SERS) bifunctional detection platform based on nanoenzymes catalyzing the tetramethylbenzidine (TMB) reaction, which innovatively introduces an aptamer recognition competition strategy and achieves an ultrasensitive detection of DR associated biomarker (VEGF). The platform employs Au@Pd nanorods (Au@Pd NRs) modified with single-stranded DNA1 (ssDNA1) as nanoenzymatic probes. Arrays of Au trioctahedra (Au TOHs) with surface-modified double-stranded structures, including aptamer strands and single-stranded DNA2 (ssDNA2), were used as capture substrates. When the target protein is present in the solution to be tested, the aptamer specifically recognizes the target protein and detaches from the surface of the capture substrate, exposing ssDNA2 and being recognized and bound by ssDNA1, allowing a large number of nanoenzymatic probes to be bound to the capture substrate, and the assay platform thus possesses excellent POD activity and SERS performance, being able to catalyze the generation of TMB with a strong SERS signal oxTMB. The platform demonstrated high detection performance, completing the assay within 14 min, with a low limit of detection (LOD) of 0.11 pg/mL. It maintained robust clinical performance even in complex serum samples, and the results were consistent with ELISA. This work offers a framework for constructing nanoenzyme-SERS bifunctional detection systems and introduces a new approach for biomarker detection.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1623332/fullnanoenzymessurface-enhanced Raman scatteringrecognition competition strategydiabetic retinopathybiomarker
spellingShingle Binbin Zeng
Xia Zong
Xinjue Dai
Lian Pan
Xiaowei Cao
Changhua Lu
Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers
Frontiers in Bioengineering and Biotechnology
nanoenzymes
surface-enhanced Raman scattering
recognition competition strategy
diabetic retinopathy
biomarker
title Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers
title_full Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers
title_fullStr Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers
title_full_unstemmed Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers
title_short Nanoenzymatic SERS bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy-related biomarkers
title_sort nanoenzymatic sers bifunctional detection platform based on recognition competition strategy for ultrasensitive detection of diabetic retinopathy related biomarkers
topic nanoenzymes
surface-enhanced Raman scattering
recognition competition strategy
diabetic retinopathy
biomarker
url https://www.frontiersin.org/articles/10.3389/fbioe.2025.1623332/full
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