Nanoparticles to Knockdown Osteoporosis-Related Gene and Promote Osteogenic Marker Expression for Osteoporosis Treatment

• Published in: ACS nano Vol. 13; no. 5; pp. 5451 - 5464
• Main Authors: Mora-Raimundo, Patricia, Lozano, Daniel, Manzano, Miguel, Vallet-Regí, María
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 28.05.2019
• Subjects: gene silencing; therapeutic co-delivery; mesoporous nanoparticles; osteoporosis; osteogenic stimulation
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.9b00241

Osteoporosis is the most common disease involving bone degeneration. Current clinical treatments are not able to offer a satisfying curative effect, so the development of effective treatments is desired. Gene silencing through siRNA delivery has gained great attention as a potential treatment in bone diseases. SOST gene inhibits the Wnt signaling pathway reducing osteoblast differentiation. Consequently, silencing SOST genes with a specific siRNA could be a potential option to treat osteoporosis. Generally, siRNAs have a very short half-life and poor transfection capacity, so an effective carrier is needed. In particular, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of nucleic acids. We took advantage of their high loading capacity to further load the pores with osteostatin, an osteogenic peptide. In this study, we developed a system based on MSNs coated with poly­(ethylenimine), which can effectively deliver SOST siRNA and osteostatin inside cells, with the consequent augmentation of osteogenic markers with a synergistic effect. This established the potential utility of MSNs to co-deliver both biomolecules to promote bone formation, this being a potential alternative to treat osteoporosis.