Tetrahedral Framework Nucleic Acid–Puerarin Complex Alleviates Osteoporosis Through the FXR/Runx2 Axis

Osteoporosis is a common disease whose primary treatment currently involves anti-osteoporosis medications. However, these drugs are often inconvenient to administer and are associated with side effects. Therefore, developing new treatments is of significant clinical importance. Puerarin (Pue) is a potential therapeutic agent for osteoporosis, but its poor solubility, low bioavailability, and instability limit its efficacy. In this study, we synthesized a tetrahedral framework nucleic acids(tFNAs)-puerarin complex (TPC) by loading puerarin onto tFNAs. TPC demonstrates enhanced cellular uptake and stability, and shows superior osteogenic activity and anti-osteoporosis effects compared to Pue alone, mediated through the FXR/Runx2 pathway. In summary, we have developed a novel nanocomplex, TPC, with promising therapeutic potential for osteoporosis.