Chen Shujing, Du Kunze, Wang Shuangqi, Liang Chunxiao, Shang Ye, Xie Xiaoyuan, Tang Ge, Li Jin, Wang Bing, Yu Xie-An, Chang Yanxu
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, China.
ACS Sens. 2023 Apr 28;8(4):1431-1439. doi: 10.1021/acssensors.2c02122. Epub 2023 Mar 6.
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 ( = 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.
糖尿病肾病(DN)是糖尿病患者主要死因之一。胱抑素C(Cys C)是肾小球滤过功能的可靠指标。因此,通过无创检测Cys C对DN进行早期预警具有紧迫性和重要意义。在本研究中,通过将2-(4-溴苯基)-3-(4-(4-(二苯胺基)苯乙烯基)苯基)富马腈(TPABDFN)的聚集诱导发光(AIE)特性与牛血清白蛋白(BSA)交联,合成了一种新型荧光传感器(BSA-AIEgen传感器),由于TPABDFN的分子内运动受限(RIM)现象,该传感器呈现“开启”状态。有趣的是,由于BSA-AIEgen传感器表面的BSA被木瓜蛋白酶水解,可发现BSA-AIEgen传感器的荧光降低,但随着作为木瓜蛋白酶抑制剂的Cys C含量增加,出现了相反的现象。因此,利用荧光差异显示成功检测到了Cys C,线性范围为12.5 ng/mL至800 ng/mL( = 0.994),检测限(LOD)为7.10 ng/mL(S/N = 3)。此外,所开发的BSA-AIEgen传感器成功地将糖尿病肾病患者与志愿者区分开来,具有高特异性、低成本和操作简单的优点。因此,有望成为一种用于监测Cys C的非免疫方法,用于糖尿病肾病的早期预警、无创诊断和药物疗效评估。