Granzyme B-responsive fluorescent probe for non-invasive early diagnosis of transplant rejection

作者全名："Gao, Tang; Yi, Luyang; Wang, Yihui; Wang, Wenyuan; Zhao, Qianqian; Song, Yuan; Ding, Mengdan; Deng, Cheng; Chen, Yihan; Xie, Yuji; Wu, Wenqian; Jin, Qiaofeng; Zhang, Li; Xie, Mingxing"

作者地址："[Gao, Tang; Yi, Luyang; Wang, Yihui; Wang, Wenyuan; Song, Yuan; Ding, Mengdan; Deng, Cheng; Chen, Yihan; Xie, Yuji; Wu, Wenqian; Jin, Qiaofeng; Zhang, Li; Xie, Mingxing] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Ultrasound Med, Wuhan 430022, Peoples R China; [Gao, Tang; Yi, Luyang; Wang, Yihui; Wang, Wenyuan; Song, Yuan; Ding, Mengdan; Deng, Cheng; Chen, Yihan; Xie, Yuji; Wu, Wenqian; Jin, Qiaofeng; Zhang, Li; Xie, Mingxing] Hubei Prov Clin Res Ctr Med Imaging, Wuhan 430022, Peoples R China; [Gao, Tang; Yi, Luyang; Wang, Yihui; Wang, Wenyuan; Song, Yuan; Ding, Mengdan; Deng, Cheng; Chen, Yihan; Xie, Yuji; Wu, Wenqian; Jin, Qiaofeng; Zhang, Li; Xie, Mingxing] Hubei Prov Key Lab Mol Imaging, Wuhan 430022, Peoples R China; [Zhao, Qianqian] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Zhao, Qianqian] Forschungszentrum Julich, Computat Biomed IAS 5 INM 9, D-52425 Julich, Germany"

通信作者："Zhang, L; Xie, MX (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Ultrasound Med, Wuhan 430022, Peoples R China."

来源：BIOSENSORS & BIOELECTRONICS

ESI学科分类：CHEMISTRY

WOS号：WOS:000983421800001

JCR分区：Q1

影响因子：10.7

年份：2023

卷号：232

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Granzyme B; Fluorescent probe; Allograft rejection; Organ transplantation

摘要："Allograft rejection has always been a major obstacle in organ transplantation. The current clinical diagnostic gold standard for allograft rejection is an invasive biopsy. However, biopsy has some limitations, such as sampling errors, risk of serious complications, and high cost. In this study, we have rationally developed an activatable fluorescent probe CYGB for imaging of granzyme B, which is a biomarker released by CD8+T cells attacking the graft. Moreover, the ability of CYGB to detect rejection early in mouse heart and skin transplantation models was evaluated. The probe CYGB consists of a caged hemicyanine-based fluorophore and a GzmB-specifically cleaved peptide substrate linked via a self-immolating spacer, p-aminobenzyl alcohol. Endogenous GzmB in CD8+ T cells specifically activated the near-infrared fluorescence (NIRF) signal of CYGB. In vivo imaging in mice skin and heart graft models, showed that CYGB preferentially accumulates in grafts, enabling early diagnosis of rejection. Moreover, CYGB enables non-invasive assessment of the level of immunosuppression in allogeneic mice treated with FK506. This study provides an alternative method for monitoring the status of allografts without biopsy."

基金机构："Natural Science Foundation of China [82202234, 81727085, 81922033, 82001852]; China Postdoctoral Science Foundation [2021M701334]; Natural Science Foundation of Hubei [SGDX20190917094601717, JCYJ20210324141216040, 2021CFA046]"

基金资助正文："This study was supported by the Natural Science Foundation of China (82202234, 81727085, 81922033, and 82001852) , and the China Postdoctoral Science Foundation (2021M701334) . The Natural Science Foundation of Hubei (2021CFA046) , the Natural Science Foundation of Hubei under Grant SGDX20190917094601717, and JCYJ20210324141216040."