Localized Nanoparticle-Mediated Delivery of miR-29b Normalizes the Dysregulation of Bone Homeostasis Caused by Osteosarcoma whilst Simultaneously Inhibiting Tumor Growth

Fiona E. Freeman, Pere Dosta, Lianne C. Shanley, Natalia Ramirez Tamez, Cristobal J. Riojas Javelly, Olwyn R. Mahon, Daniel J. Kelly, Natalie Artzi

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Resum

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.

Idioma originalAnglès
Número d’article2207877
RevistaAdvanced Materials
Volum35
Número23
DOIs
Estat de la publicacióPublicada - 8 de juny 2023
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