Royal College of Surgeons in Ireland
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Localized nanoparticle-mediated delivery of mir-29b normalizes the dysregulation of bone homeostasis caused by osteosarcoma whilst simultaneously inhibiting tumor growth.pdf (6.86 MB)
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Localized nanoparticle-mediated delivery of miR-29b normalizes the dysregulation of bone homeostasis caused by osteosarcoma whilst simultaneously inhibiting tumor growth

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journal contribution
posted on 2023-05-15, 14:51 authored by Fiona E Freeman, Pere Dosta, Lianne C Shanley, Natalia Ramirez Tamez, Cristobal J Riojas Javelly, Olwyn R Mahon, Daniel KellyDaniel Kelly, Natalie Artzi

Patients diagnosed with osteosarcoma undergo extensive surgical intervention and chemotherapy resulting in dismal prognosis and compromised quality of life owing to poor bone regeneration, which is further compromised with chemotherapy delivery. This study aims to investigate if localized delivery of miR-29b-which is shown to promote bone formation by inducing osteoblast differentiation and also to suppress prostate and cervical tumor growth-can suppress osteosarcoma tumors whilst simultaneously normalizing the dysregulation of bone homeostasis caused by osteosarcoma. Thus, the therapeutic potential of microRNA (miR)-29b is studied to promote bone remodeling in an orthotopic model of osteosarcoma (rather than in bone defect models using healthy mice), and in the context of chemotherapy, that is clinically relevant. A formulation of miR-29b:nanoparticles are developed that are delivered via a hyaluronic-based hydrogel to enable local and sustained release of the therapy and to study the potential of attenuating tumor growth whilst normalizing bone homeostasis. It is found that when miR-29b is delivered along with systemic chemotherapy, compared to chemotherapy alone, the therapy provided a significant decrease in tumor burden, an increase in mouse survival, and a significant decrease in osteolysis thereby normalizing the dysregulation of bone lysis activity caused by the tumor. 

Funding

European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 839150

Gillian Reny Stepping Strong Center for Trauma Innovation

Johnson & Johnson

History

Comments

The original article is available at https://onlinelibrary.wiley.com/

Published Citation

Freeman FE. et al Localized nanoparticle-mediated delivery of miR-29b normalizes the dysregulation of bone homeostasis caused by osteosarcoma whilst simultaneously inhibiting tumor growth. Adv Mater. 2023;35(23):e2207877

Publication Date

30 March 2023

PubMed ID

36994935

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine

Publisher

Wiley-VCH GmbH

Version

  • Published Version (Version of Record)