Development of an activity-based ratiometric electrochemical substrate for measuring circulating dipeptidyl peptidase-IV/CD26 in whole blood samples.

Journal: Biosensors & bioelectronics
Published Date:

Abstract

Dipeptidyl peptidase-IV (DPP-IV) is a circulating blood biomarker that diagnose pancreatic and thyroid cancers, as well as type 2 diabetes. Although current DPP-IV detection methods show promise, real-time detection in whole blood is limited, as blood samples require tedious pre-treatment. To overcome these limitations, a DPP-IV targeted electrochemical substrate, DPPLPOH (DiPeptidyl Peptidase Latent Probe-OH (with Hydroxyl group)), was designed. When coupled with an electrochemical analytical method, this substrate enabled direct and convenient detection of DPP-IV in complex biofluids, including whole blood samples. In these assays, DPP-IV selectively hydrolyzed DPPLPOH, which underwent a self-immolative reaction to generate a masked electrochemically sensitive amino ferrocene reporter (AFOH). This electrochemical analytical tool demonstrated excellent sensing performance, characterized by exceptional enzyme binding properties. DPPLPOH showed excellent sensitivity and selectivity, with a detection limit of 0.021 ng/mL and a broad linear detection range of 0.1-100 ng/mL. The probe was specific to DPP-IV without interference from other electroactive species, enzymes, or hydrolases. Furthermore, DPPLPOH enabled real-time monitoring of DPP-IV activity on tumor cell surfaces and direct tracking of DPP-IV concentration in whole blood without a tedious separation process. This method may be a valuable tool in the early detection of pancreatic and thyroid cancers and in post-treatment surveillance.

Authors

  • Namasivayam Kumaragurubaran
    Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 106, Taiwan, ROC; Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, 106, Taiwan, ROC.
  • Hou Po Yun
    Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 106, Taiwan, ROC; Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, 106, Taiwan, ROC.
  • Antanas Zinovicius
    Department of Nanotechnology, State Research Institute Centre for Physical Sciences and Technology (FTMC), Sauletekio av. 3, 10257, Vilnius, Lithuania.
  • Sheng-Tung Huang
    Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 106, Taiwan, ROC; Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, 106, Taiwan, ROC; High-Value Biomaterials Research and Commercialization Center, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd., 10608, Taipei, Taiwan, ROC. Electronic address: ws75624@ntut.edu.tw.
  • Ponnusamy Arul
    Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 106, Taiwan, ROC; Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, 106, Taiwan, ROC.
  • Hsin-Yi Lin
    Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 106, Taiwan, ROC.
  • Ou Min-Shin
    Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 106, Taiwan, ROC.
  • Inga Morkvenaite-Vilkonciene
    Department of Nanotechnology, State Research Institute Centre for Physical Sciences and Technology (FTMC), Sauletekio av. 3, 10257, Vilnius, Lithuania. Electronic address: inga.vilkonciene@ftmc.lt.

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