Noninvasive Early Diagnosis of Allograft Rejection by a Granzyme B Protease Responsive NIR-II Bioimaging Nanosensor

Angew Chem Int Ed Engl. 2023 Jun 5;62(23):e202301696. doi: 10.1002/anie.202301696. Epub 2023 May 3.

Abstract

Early diagnosis of allograft rejection helps to improve the immune-related management of transplant recipients. The clinically-used core needle biopsy method is invasive and subject to sampling error. In vivo fluorescence imaging for monitoring immune-related processes has the advantages of non-invasiveness, fast feedback and high sensitivity. Herein, we report a responsive second near-infrared (NIR-II) fluorescent nanosensor (ErGZ) to detect early allograft rejection. ErGZ allows ratiometric in vivo fluorescence sensing of granzyme B, which is overexpressed in recipients' T cells during the onset of rejection. The sensor demonstrates efficacious detection of allograft rejection with high sensitivity and specificity, which accomplishes non-invasive diagnosis of rejection in skin and deep buried islets transplant mice models 2 d and 5 d earlier than biopsy, by in vivo fluorescence imaging and urinary detection, respectively, providing a valuable approach for therapeutical management.

Keywords: Gryme B Protease; NIR-II Fluorescence; Ratio Imaging; Tralant Rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • Biopsy
  • Granzymes
  • Mice
  • T-Lymphocytes*
  • Transplantation, Homologous

Substances

  • Granzymes