Smart osteoclasts targeted nanomedicine based on amorphous CaCO 3 for effective osteoporosis reversal

Osteoporosis is characterized by an imbalance in bone homeostasis, resulting in the excessive dissolution of bone minerals due to the acidified microenvironment mediated by overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential in reversing osteoporosis by inhibiting oste...

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Bibliographic Details
Published inJournal of nanobiotechnology Vol. 22; no. 1; p. 153
Main Authors Yu, Biao, Gao, Qianmin, Sheng, Shihao, Zhou, Fengjin, Geng, Zhen, Wei, Yan, Zhang, Hao, Hu, Yan, Wang, Sicheng, Huang, Jianping, Li, Mengmeng, Su, Jiacan
Format Journal Article
LanguageEnglish
Published England 05.04.2024
Subjects
Animals
Bone and Bones - pathology
Bone Resorption - drug therapy
Cell Differentiation
Mice
Nanomedicine
Osteoclasts
Osteoporosis - drug therapy
Osteoporosis
Acidic microenvironment
Oroxylin A
pH responsiveness
Synergistic therapy
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Summary:Osteoporosis is characterized by an imbalance in bone homeostasis, resulting in the excessive dissolution of bone minerals due to the acidified microenvironment mediated by overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential in reversing osteoporosis by inhibiting osteoclast-mediated bone resorption. The limited water solubility and lack of targeting specificity hinder the effective accumulation of Oroxylin A within the pathological environment of osteoporosis. Osteoclasts' microenvironment-responsive nanoparticles are prepared by incorporating Oroxylin A with amorphous calcium carbonate (ACC) and coated with glutamic acid hexapeptide-modified phospholipids, aiming at reinforcing the drug delivery efficiency as well as therapeutic effect. The obtained smart nanoparticles, coined as OAPLG, could instantly neutralize acid and release Oroxylin A in the extracellular microenvironment of osteoclasts. The combination of Oroxylin A and ACC synergistically inhibits osteoclast formation and activity, leading to a significant reversal of systemic bone loss in the ovariectomized mice model. The work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis.
ISSN:1477-3155