A bone-targeting delivery platform based on mesoporous silica loaded with piR7472 for the treatment of osteoporosis

Promoting osteogenic differentiation and inhibiting osteoclast formation remain significant challenges in the treatment of osteoporosis. With the growing understanding of osteoporosis, increasing literature has highlighted the regulatory role of m6A methylation in this condition. However, there is currently no reliable method to stably regulate cellular m6A methylation levels. Here, we report a novel approach utilizing alendronate (aln)-modified mesoporous silica nanoparticles (MSNs) to deliver sodium bicarbonate and piR7472, modulating cellular behavior. Our experimental results demonstrate that Aln modification enables the nanoparticles to stably target hydroxyapatite, thereby accumulating in osteoporotic regions. Sodium bicarbonate suppresses osteoclastogenesis, while piR7472 enhances m6A methylation, promoting osteogenic differentiation of bone marrow stromal cells (BMSCs). Computed tomography (CT) and hematoxylin and eosin (HE) staining showed that after 2 weeks of treatment with MSNs-Na@piR7472, cortical bone thickened, trabecular bone density increased, collagen fiber thickness improved, and both the number and staining area of osteoclasts were significantly reduced. These findings indicate a marked improvement in osteoporosis.