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Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.

Publication ,  Journal Article
Hoque, J; Shih, Y-RV; Zeng, Y; Newman, H; Sangaj, N; Arjunji, N; Varghese, S
Published in: Biomaterials
June 2021

Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous presence of adenosine receptors in different organs and the short half-life of adenosine in circulation. Towards this, we have developed a bone-targeting nanocarrier and determined its potential for systemic administration of adenosine. The nanocarrier, synthesized via emulsion suspension photopolymerization, is comprised of hyaluronic acid (HA) copolymerized with phenylboronic acid (PBA), a moiety that can form reversible bonds with adenosine. The bone binding affinity of the nanocarrier was achieved by alendronate (Aln) conjugation. Nanocarriers functionalized with the alendronate (Aln-NC) showed a 45% higher accumulation in the mice vertebrae in vivo compared to those lacking alendronate molecules (NCs). Systemic administration of adenosine via bone-targeting nanocarriers (Aln-NC) attenuated bone loss in ovariectomized (OVX) mice. Furthermore, bone tissue of mice treated with adenosine-loaded Aln-NC displayed trabecular bone characteristics comparable to healthy controls as shown by microcomputed tomography, histochemical staining, bone labeling, and mechanical strength. Overall, our results demonstrate the use of a bone-targeting nanocarrier towards systemic administration of adenosine and its application in treating bone degenerative diseases such as osteoporosis.

Duke Scholars

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

June 2021

Volume

273

Start / End Page

120819

Location

Netherlands

Related Subject Headings

  • X-Ray Microtomography
  • Rats, Sprague-Dawley
  • Rats
  • Ovariectomy
  • Osteoporosis
  • Mice
  • Humans
  • Female
  • Bone and Bones
  • Bone Density Conservation Agents
 

Citation

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Hoque, J., Shih, Y.-R., Zeng, Y., Newman, H., Sangaj, N., Arjunji, N., & Varghese, S. (2021). Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss. Biomaterials, 273, 120819. https://doi.org/10.1016/j.biomaterials.2021.120819
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

June 2021

Volume

273

Start / End Page

120819

Location

Netherlands

Related Subject Headings

  • X-Ray Microtomography
  • Rats, Sprague-Dawley
  • Rats
  • Ovariectomy
  • Osteoporosis
  • Mice
  • Humans
  • Female
  • Bone and Bones
  • Bone Density Conservation Agents