LAUSR

pH is a critical indicator of bone physiological function and disease status; however, noninvasive and real-time sensing of bone pH in vivo has been a challenge. Here, we synthesized a bone pH sensor by labeling alendronate with the H+-sensitive dye fluorescein isothiocyanate (Aln-FITC). Aln-FITC showed selective affinity for hydroxyapatite (HAp) rather than other calcium materials. An in vivo biodistribution study showed that Aln-FITC can be rapidly and specifically delivered to rat bones after caudal vein injection, and the fluorescence lasted for at least 12 h. The fluorescence intensity of Aln-FITC binding to HAp linearly decreased when the pH changed from 6 to 12. This finding was further confirmed on bone blocks and perfused bone when the pH changed from 6.8 to 7.4, indicating unique pH-responsive characteristics in the bone microenvironment. Aln-FITC was then preliminarily applied to evaluate the changes in bone pH in a nude mouse acidosis model. Our results demonstrated that Aln-FITC might have the potential for minimally invasive and real-time in vivo bone pH sensing in preclinical studies of bone healing, metabolism, and cancer mechanisms.