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Classical drug treatments for osteoporotic bone defects have unsatisfactory efficacy owing to side effects and imprecise delivery problems. In this study, a magnetic aggregation\u2010induced bone\u2010targeting poly(lactic\u2010co\u2010glycolic acid, PLGA)\u2010based nanocarrier (ZOL\u2010PLGA@Yoda1\/SPIO) is synthesized to realize dual\u2010targeted delivery and precise Piezo1\u2010activated therapy for osteoporotic bone defects. Piezo1 is an important mechanotransducer that plays a key role in regulating bone homeostasis. To achieve dual\u2010targeting properties, ZOL\u2010PLGA@Yoda1\/SPIO is fabricated using zoledronate (ZOL)\u2010decorated PLGA, superparamagnetic iron oxide (SPIO), and Piezo1\u2010activated molecule Yoda1 via the emulsion solvent diffusion method. Bone\u2010targeting molecular mediation and magnetic aggregation\u2010induced properties can jointly and effectively achieve precise delivery to localized bone defects. Moreover, Yoda1 loading enables targeted and efficient mimicking of mechanical signals and activation of Piezo1. Experiments in vivo and in vitro demonstrate that ZOL\u2010PLGA@Yoda1\/SPIO can activate Piezo1 in bone defect areas of osteoporotic mice, improve osteogenesis through YAP\/\u03b2\u2010catenin signaling axis, promote a well\u2010coordinated osteogenesis\u2013angiogenesis coupling, and significantly accelerate bone reconstruction within the defects without noticeable side effects. Overall, this novel dual\u2010targeting nanocarrier provides a potentially effective strategy for the clinical treatment of osteoporotic bone defects.<\/jats:p>","DOI":"10.1002\/adma.202312081","type":"journal-article","created":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T08:32:01Z","timestamp":1702715521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Magnetic Aggregation\u2010Induced Bone\u2010Targeting Nanocarrier with Effects of Piezo1 Activation and Osteogenic\u2013Angiogenic Coupling for Osteoporotic Bone Repair"],"prefix":"10.1002","volume":"36","author":[{"given":"Haitao","family":"Guan","sequence":"first","affiliation":[{"name":"The School of Medicine Nankai University  Tianjin 300071 China"},{"name":"Department of Orthopaedic Surgery The Third Hospital of Hebei Medical University  Shijiazhuang Hebei 050051 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