A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosisOAMEDLINE
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 ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.
Yong Li;Zhengwen Cai;Wenjuan Ma;Long Bai;En Luo;Yunfeng Lin;
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 ChinaState 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 ChinaDepartment of Oral and Maxillofacial Surgery,Affiliated Stomatological Hospital,Southwest Medical University,Luzhou,Sichuan 646000,PR ChinaState 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
临床医学
curcuminosteoporosisdiabetic
《Bone Research》 2024 (001)
P.227-239 / 13
This research was financially supported by the National Key R&D Program of China(2019YFA0110600);the National Natural Science Foundation of China(82370932,81970917,82370929,81970916,81800947,82101077);the Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202102,RD03202302);Sichuan Science and Technology Program(2022NSFSC0002);Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021).
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