An APN-Activated Chemiluminescent Probe for Image-Guided Surgery of Malignant Tumors

Developing smart molecular probes for assisting surgeons to precisely detect cancerous tissues and to completely remove all of them during the surgery is urgently required. Conventional fluorescent probes allow for tumor detection but with limited signal-to-noise ratio. Herein, an aminopeptidase N/CD13 (APN)-activated chemiluminescent probe (APN-ACLP) is reported for sensitive imaging and precise resection of malignant tumors. The APN-ACLP probe is based on acryl-substituted phenoxy-dioxetane that is coupled with an APN-cleavable substrate via a self-immolative linker. Upon activation by APN through specific hydrolysis reaction, APN-ACLP generates spontaneously chemiluminescence signal, which offers a possibility to sensitively search tumors by simply spraying APN-ACLP on the suspicious sites. Animal imaging studies reveal that a sufficient signal contrast between the cancerous tissues and the normal counterparts can be achieved within 5 min, which can allow for rapid detection and surgical resection of tumors, particularly tiny metastatic lesions in mice model, under the guidance of chemiluminescence imaging, well manifesting its potential for image-guided surgery of malignant tumors.