A Non-Immunized and BSA-Template Aggregation-Induced Emission Sensor for Noninvasive Detection of Cystatin C in the Clinical Diagnosis of Diabetes Nephropathy

ACS Sens. 2023 Apr 28;8(4):1431-1439. doi: 10.1021/acssensors.2c02122. Epub 2023 Mar 6.

Abstract

Diabetes nephropathy (DN) is one of the main causes of death in patients with diabetes. Cystatin C (Cys C) is a reliable indicator of glomerular filtration function. Therefore, it is urgent and meaningful to obtain early warning of DN by noninvasive measurement of Cys C. In this investigation, a novel fluorescence sensor (BSA-AIEgen sensor) was synthesized by cross-linking the aggregation-induced emission (AIE) characteristics of 2-(4-bromophenyl)-3-(4-(4-(diphenylamino) styryl) phenyl) fumaronitrile (TPABDFN) and bovine serum albumin (BSA), which exhibited the "On" state owing to the restriction of the intramolecular motions (RIM) phenomenon of TPABDFN. Intriguingly, a decrease in fluorescence of BSA-AIEgen sensors could be found owing to BSA on the surface of BSA-AIEgen sensor hydrolyzed by papain, but a reverse phenomenon emerged with the increase of Cys C content as the inhibitor of papain. Hence, Cys C was successfully detected by employing the fluorescent differential display and the linear range was from 12.5 ng/mL to 800 ng/mL (R2 = 0.994) with the limit of detection (LOD) of 7.10 ng/mL (S/N = 3). Further, the developed BSA-AIEgen sensor successfully differentiates patients with diabetes nephropathy from volunteers with the advantages of high specificity, low cost, and simple operation. Accordingly, it is expected to become a non-immunized method to monitor Cys C for the early warning, noninvasive diagnosis, and drug efficacy evaluation of diabetes nephropathy.

Keywords: Aggregation-induced emission; Bovine serum albumin; Cystatin C; Diabetes nephropathy; Fluorescent sensors; Papain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystatin C*
  • Diabetes Mellitus* / diagnosis
  • Humans
  • Limit of Detection
  • Papain
  • Serum Albumin, Bovine

Substances

  • Cystatin C
  • Serum Albumin, Bovine
  • Papain