Near-Infrared Ratiometric Hemicyanine-Based pH Fluorescence Probe with Bone Targetability for Monitoring Bone Resorption

• Published in: Analytical chemistry (Washington) Vol. 95; no. 7; pp. 3736 - 3745
• Main Authors: Meng, Yiling, Zhao, Delu, Yang, Xingye, Li, Yixuan, Liu, Bohui, Zhang, Zijie, Cui, Shuyue, Wei, Fulan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.02.2023
• Subjects: Analytical chemistry; Biocompatibility; Bone and Bones; Bone imaging; Bone resorption; Bone Resorption - diagnostic imaging; Chemistry; Cytotoxicity; Fluorescence; Fluorescent Dyes - toxicity; Fluorescent indicators; Health services; HeLa Cells; Humans; Hydrogen-Ion Concentration; I.R. radiation; In vitro methods and tests; In vivo methods and tests; Interference; Jaw; Monitoring; Orthodontics; Osteonecrosis; Performance tests; pH effects; Real time; Sensitivity; Toxicity testing
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.2c04786

Accurate detection of bone resorption is extremely important in the orthodontic treatment process as it can provide a basis for clinical treatment strategies. Recently, pH-responsive fluorescence probes have received tremendous attention in bone resorption monitoring owing to their high sensitivity, good specificity, and in situ and real-time detection capabilities, but there are still some shortcomings like the increase in the risk of osteonecrosis of the jaw by use of bisphosphonate as the bone-targeting moiety and the insufficient monitoring accuracy due to susceptibility to interference. Herein, we designed and synthesized a near-infrared ratiometric hemicyanine-based pH fluorescence probe (Hcy-Asp6) with fluorescence-imaging and pH-determining capabilities, and bone targetability for more reliably and safely monitoring the bone resorption in orthodontic treatment. In vitro optical performance tests of Hcy-Asp6 revealed that the probe had high sensitivity, excellent photostability, reversibility, and strong resistance to interference, and the probe suggested excellent bone-binding ability and biocompatibility in the bone-targeting evaluation and the cytotoxicity test. Furthermore, in vitro and in vivo bone resorption monitoring assays demonstrated that this probe can detect bone resorption by fluorescence imaging and quantitative monitoring of pH associated with the bone resorption. Thus, the results indicated that this probe possessing bone targetability and accurate bone resorption-monitoring capability has an extraordinarily great clinical potential to be employed for real-time monitoring of bone resorption in orthodontic treatment and could also serve as a reference in bone resorption monitoring for other bone resorption-related diseases.