A pH-sensitive carbonic anhydrase IX-targeted near-infrared probe for fluorescent sensing and imaging of hypoxic osteosarcoma

Osteosarcoma (OS) is the most prevalent carcinoma of the skeletal system with high rate of mortality and morbidity. The rate of limb salvage and overall survival for patients with osteosarcoma can increase if the lesion can be detected early and effective interventional therapies. Previous works reported that carbonic anhydrase IX (CA IX) is an important functional protein in the acidification of the tumor microenvironment and widely exists on the cell membrane surface of hypoxic tumors, thus it can be considered as a potential tumor biomarker. High CA IX level is also related to poor prognosis and invasion of OS. Herein we utilized the overexpression of proto-oncogenic CA IX in hypoxic tumors to develop a novel pH-sensitive near-infrared imaging probe: ABSi-783 by combining CA IX inhibitor ABSi with the tricarbocyanine IR783. The probe has exceptional merits with an increasing near-infrared emission with pKa values of ca. 5.49 in Britton-Robinson buffers from pH 3.00-11.00, and can well sense changes of overexpression level of the biomarker CA IX in the hypoxic environment of 143B cells. In addition, it has high selectivity to target osteosarcoma imaging and detect pH changes in vitro without significant toxicity. It has been demonstrated that the probe can be used well in early targeted diagnosis of osteosarcoma and extended to indicate and monitor tumors in surgical treatment.