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A DNA tetrahedron-based ferroptosis-suppressing nanoparticle:superior delivery of curcumin and alleviation of diabetic osteoporosis

摘要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.

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作者 Yong Li [1] Zhengwen Cai [2] Wenjuan Ma [2] Long Bai [3] En Luo [2] Yunfeng Lin [4] 学术成果认领
作者单位 State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan 610041,PR China;Department of Oral and Maxillofacial Surgery,Affiliated Stomatological Hospital,Southwest Medical University,Luzhou,Sichuan 646000,PR China [1] State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan 610041,PR China [2] Department of Oral and Maxillofacial Surgery,Affiliated Stomatological Hospital,Southwest Medical University,Luzhou,Sichuan 646000,PR China [3] State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan 610041,PR China;Sichuan Provincial Engineering Research Center of Oral Biomaterials,Chengdu,Sichuan 610041,China [4]
栏目名称 ORIGINAL ARTICLES
DOI 10.1038/s41413-024-00319-7
发布时间 2024-05-21
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骨研究(英文版)

骨研究(英文版)

2024年12卷1期

227-239页

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