biostudies-literatureNewman HNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNIA NIH HHSNIAMS NIH HHSNational Science Foundation5340-5355https://www.ebi.ac.uk/biostudies/studies/S-EPMC9894097biostudies-literatureUnknown10(18)Bone tissue undergoes continuous remodeling <i>via</i> osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An imbalance in this process with enhanced osteoclastic activity can lead to excessive bone resorption, resulting in bone thinning. Once activated, osteoclasts bind to the bone surface and acidify the local niche. This acidic environment could serve as a potential trigger for the delivery of therapeutic agents into the osteoporotic bone tissue. To this end, we developed a pH-responsive nanocarrier-based drug delivery system that binds to the bone tissue and delivers an osteoanabolic molecule, adenosine. Adenosine is incorporated into a hyaluronic acid (HA)-based nanocarrier through a pH-sensitive ketal group. The HA-nanocarrier is further functionalized with alBiomaterials sciencepH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss.PMC9894097R01 AG074491RO1 AR079189R01 AR071552ECCS-1542015DMR-1726294R01 AR079189RO1 AR071552Ko UVarghese SNewman HHoque JShih YVMarushack GGonzales GfalsepH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss.Bone tissue undergoes continuous remodeling <i>via</i> osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An imbalance in this process with enhanced osteoclastic activity can lead to excessive bone resorption, resulting in bone thinning. Once activated, osteoclasts bind to the bone surface and acidify the local niche. This acidic environment could serve as a potential trigger for the delivery of therapeutic agents into the osteoporotic bone tissue. To this end, we developed a pH-responsive nanocarrier-based drug delivery system that binds to the bone tissue and delivers an osteoanabolic molecule, adenosine. Adenosine is incorporated into a hyaluronic acid (HA)-based nanocarrier through a pH-sensitive ketal group. The HA-nanocarrier is further functionalized with al2022-01-01T00:00:00Z2022 Sep2025-04-04T21:13:53.014Z2025-04-04T21:13:53.014ZS-EPMC98940973592951610.1039/d2bm00843b