Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal
Abstract Background 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 osteoporosi...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-04-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02412-9 |
| _version_ | 1827291350364585984 |
|---|---|
| author | Biao Yu Qianmin Gao Shihao Sheng Fengjin Zhou Zhen Geng Yan Wei Hao Zhang Yan Hu Sicheng Wang Jianping Huang Mengmeng Li Jiacan Su |
| author_facet | Biao Yu Qianmin Gao Shihao Sheng Fengjin Zhou Zhen Geng Yan Wei Hao Zhang Yan Hu Sicheng Wang Jianping Huang Mengmeng Li Jiacan Su |
| author_sort | Biao Yu |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusion The work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis. |
| first_indexed | 2024-04-24T12:36:34Z |
| format | Article |
| id | doaj.art-cd7c9f8672e249b3912fc45433b57249 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-24T12:36:34Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-cd7c9f8672e249b3912fc45433b572492024-04-07T11:29:22ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122111510.1186/s12951-024-02412-9Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversalBiao Yu0Qianmin Gao1Shihao Sheng2Fengjin Zhou3Zhen Geng4Yan Wei5Hao Zhang6Yan Hu7Sicheng Wang8Jianping Huang9Mengmeng Li10Jiacan Su11Institute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical UniversityDepartment of Orthopedics, Honghui Hospital, Xi’an Jiao Tong UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversitySchool of Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityAbstract Background 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. Results 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. Conclusion The work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis.https://doi.org/10.1186/s12951-024-02412-9pH responsivenessOroxylin AOsteoporosisAcidic microenvironmentSynergistic therapy |
| spellingShingle | Biao Yu Qianmin Gao Shihao Sheng Fengjin Zhou Zhen Geng Yan Wei Hao Zhang Yan Hu Sicheng Wang Jianping Huang Mengmeng Li Jiacan Su Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal Journal of Nanobiotechnology pH responsiveness Oroxylin A Osteoporosis Acidic microenvironment Synergistic therapy |
| title | Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal |
| title_full | Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal |
| title_fullStr | Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal |
| title_full_unstemmed | Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal |
| title_short | Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal |
| title_sort | smart osteoclasts targeted nanomedicine based on amorphous caco3 for effective osteoporosis reversal |
| topic | pH responsiveness Oroxylin A Osteoporosis Acidic microenvironment Synergistic therapy |
| url | https://doi.org/10.1186/s12951-024-02412-9 |
| work_keys_str_mv | AT biaoyu smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT qianmingao smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT shihaosheng smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT fengjinzhou smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT zhengeng smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT yanwei smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT haozhang smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT yanhu smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT sichengwang smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT jianpinghuang smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT mengmengli smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal AT jiacansu smartosteoclaststargetednanomedicinebasedonamorphouscaco3foreffectiveosteoporosisreversal |