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

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.