Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal

Biao Yu; Qianmin Gao; Shihao Sheng; Fengjin Zhou; Zhen Geng; Yan Wei; Hao Zhang; Yan Hu; Sicheng Wang; Jianping Huang; Mengmeng Li; Jiacan Su

doi:10.1186/s12951-024-02412-9

Smart osteoclasts targeted nanomedicine based on amorphous CaCO₃ for effective osteoporosis reversal

J Nanobiotechnology. 2024 Apr 5;22(1):153. doi: 10.1186/s12951-024-02412-9.

Authors

Biao Yu^#^{1

2

3

4}, Qianmin Gao^#^{1

2

3}, Shihao Sheng^#⁵, Fengjin Zhou^#⁶, Zhen Geng^{1

2}, Yan Wei^{1

2}, Hao Zhang^{1

2}, Yan Hu^{1

2

7}, Sicheng Wang^{8

9

10

11}, Jianping Huang^{12

13

14}, Mengmeng Li^{15

16}, Jiacan Su^{17

18

19}

Affiliations

¹ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
² Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China.
³ School of Medicine, Shanghai University, Shanghai, 200444, China.
⁴ Second Affiliated Hospital, Shanghai University, Wenzhou, 325000, China.
⁵ Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
⁶ Department of Orthopedics, Honghui Hospital, Xi'an Jiao Tong University, Xi'an, 710000, China.
⁷ Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
⁸ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China. w.s.c@sina.com.
⁹ Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China. w.s.c@sina.com.
¹⁰ School of Medicine, Shanghai University, Shanghai, 200444, China. w.s.c@sina.com.
¹¹ Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200941, China. w.s.c@sina.com.
¹² School of Medicine, Shanghai University, Shanghai, 200444, China. dr.hjp@163.com.
¹³ Second Affiliated Hospital, Shanghai University, Wenzhou, 325000, China. dr.hjp@163.com.
¹⁴ Department of Neurology, Wenzhou Central Hospital, Wenzhou, 325000, China. dr.hjp@163.com.
¹⁵ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China. mengmengli@shu.edu.cn.
¹⁶ Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China. mengmengli@shu.edu.cn.
¹⁷ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China. jiacansu@shu.edu.cn.
¹⁸ Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China. jiacansu@shu.edu.cn.
¹⁹ Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. jiacansu@shu.edu.cn.

^# Contributed equally.

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.

Keywords: Acidic microenvironment; Oroxylin A; Osteoporosis; Synergistic therapy; pH responsiveness.

MeSH terms

Animals
Bone Resorption* / drug therapy
Bone and Bones / pathology
Cell Differentiation
Mice
Nanomedicine
Osteoclasts
Osteoporosis* / drug therapy

Abstract

MeSH terms

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