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

We report a non-invasive imaging strategy for sensing transplant rejection based on the granzyme B protease activity by using a ratiometric second near-infrared (NIR-II) nanosensor, ErGZ. ErGZ accomplished early detection of allograft rejection at 5 d post-operation by both in vivo fluorescence imaging and in vitro urinary excretion measurement, providing a promising alternative to biopsy for routine screening of early immunological rejection.

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.

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