Oral delivery of teriparatide utilizing biocompatible transferrin-engineered MOF nanoparticles for osteoporosis therapy.

Osteoporosis, a systemic skeletal disorder characterized by reduced bone density and increased fracture risk, poses a significant global health challenge. While teriparatide (TRP), a first-line anabolic peptide drug, demonstrates substantial therapeutic benefits in osteoporosis management, its clinical use is restricted by the necessity for daily subcutaneous administration, leading to suboptimal patient compliance. To overcome this limitation, we developed an orally deliverable TRP formulation using biocompatible metal-organic framework nanoparticles (MOF-808 NPs) co-loaded with TRP and functionalized with transferrin targeting ligands (M@P@T NPs). The rationally designed nanoporous architecture coupled with transferrin surface modification synergistically protects TRP from acidic and enzymatic degradation in harsh gastrointestinal environments, while realizing controlled release of TRP in the phosphate-rich bloodstream. Leveraging the overexpression of transferrin receptors (TfR) on intestinal epithelial cells, the nanosystem facilitates receptor-mediated transcellular transport, enabling efficient systemic delivery of TRP with high oral bioavailability. After the one-month oral administration of low-dose M@P@T (200 μg kg-1·day-1) to osteoporosis model mice, therapeutic outcomes comparable to those achieved with subcutaneous TRP injections were observed, including increased bone mineral density, improved trabecular structure, and significant alleviation of osteoporosis symptoms. These findings suggest that this MOF-based oral TRP strategy has great potential for simplifying and improving the treatment of osteoporosis.