Diabetic osteoporosis (DOP) is a significant complication that poses continuous threat to the bone health of patients with diabetes; however, currently, there are no effective treatment strategies. In patients with diabetes, the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells (BMSCs), leading to significant skeletal changes. To address this issue, we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP. We synthesized ferroptosis-suppressing nanoparticles, which could deliver curcumin, a natural compound, to the bone marrow using tetrahedral framework nucleic acid (tFNA). This delivery system demonstrated excellent curcumin bioavailability and stability, as well as synergistic properties with tFNA. Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) pathway, inhibiting ferroptosis, promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment, reducing trabecular loss, and increasing bone formation. These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosis-suppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

糖尿病骨质疏松症（DOP）是一种严重的并发症，对糖尿病患者的骨骼健康构成持续威胁；然而，目前尚无有效的治疗策略。在糖尿病患者中，铁死亡水平增加会影响骨间充质干细胞（BMSC）的成骨定向和分化，导致显着的骨骼变化。为了解决这个问题，我们旨在针对铁死亡并提出一种治疗 DOP 的新治疗方法。我们合成了抑制铁死亡的纳米粒子，它可以使用四面体框架核酸（tFNA）将天然化合物姜黄素输送到骨髓。该递送系统表现出优异的姜黄素生物利用度和稳定性，以及与 tFNA 的协同特性。体外和体内实验均表明，纳米颗粒可以通过激活核因子E2相关因子2（NRF2）/谷胱甘肽过氧化物酶4（GPX4）途径增强线粒体功能，抑制铁死亡，促进糖尿病微环境中BMSCs的成骨分化，减少小梁损失，增加骨形成。这些发现表明，含有姜黄素的 DNA 四面体基铁死亡抑制纳米颗粒在治疗 DOP 和其他铁死亡相关疾病方面具有广阔的潜力。