Near-infrared Chemiluminescence Imaging of Chemotherapy-induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) has a high prevalence but is poorly managed for cancer patients due to the lack of reliable and sensitive diagnostic techniques. Molecular optical imaging can provide a noninvasive way for real-time monitoring of CIPN. However, this has not been reported, likely due to the absence of optical probes capable of imaging deep into the spinal canal and possessing sufficient sensitivity for minimal dosage through local injection into the dorsal root ganglia. Herein, we synthesize a near-infrared (NIR) chemiluminophore (MPBD) with a chemiluminescence quantum yield higher than other reported probes and develop it into a NIR activatable chemiluminescent probe (CalCL) for in vivo imaging of CIPN. CalCL is constructed by caging MPBD with calpain-cleavable peptide moiety while conjugating polyethylene glycol chain to endow water solubility. Due to the deep-tissue penetration of chemiluminescence and specific turn-on response of CalCL towards calpain (a hallmark of CIPN), it allows for sensitive detection of paclitaxel-mediated CIPN in living mice, which is unattainable by fluorescence imaging. This study thus not only develops a highly efficient chemiluminescent probe but also presents the first optical imaging approach toward high-throughput screening of neurotoxic drugs. This article is protected by copyright. All rights reserved.