Curcumin delivery using tetrahedral framework nucleic acids enhances bone regeneration in osteoporotic rats

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2023-09, Vol.472, p.144978, Article 144978
• Main Authors: Bai, Long, Feng, Maogeng, Li, Qiumei, Zhao, Yuxuan, Zhang, Geru, Cai, Zhengwen, Xiao, Jingang, Lin, Yunfeng
• Format: Article
• Language: English
• Subjects: Bone regeneration; Curcumin; Drug delivery; Osteoporosis; Tetrahedral framework nucleic acids
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2023.144978

tFNAs carrys Cur into BMSCs for promoting osteogenesis by inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK), regulating the expression of anti-apoptotic and pro-apoptotic proteins, and resisting the apoptosis induced by TNF-α. [Display omitted] •tFNAs/Cur system was developed and applied to promote bone healing.•tFNAs/Cur have excellent stability, and biocompatibility.•tFNAs/Cur enhance the anti-apoptotic ability of BMSCs. Osteoporosis is an age-related disorder characterized by progressive bone loss and impaired bone regeneration following surgery. The key to the treatment of osteoporosis is the ability to promote bone differentiation of bone marrow mesenchymal stem cells (BMSCs). Curcumin (Cur) is a class of flavonoids with antioxidant and anti-apoptotic ability to promote osteogenesis in osteoporosis. However, Cur has deficiencies such as low cell entry efficiency, easy degradation and hydrophobicity, and new drug delivery strategies are urgently needed to improve the application prospects of Cur. Tetrahedral framework nucleic acids (tFNAs) are a class of anti-inflammatory and antioxidant nanomedicines with spatial structure, as well as small molecule drug delivery systems with good biosafety. tFNAs can bind herbal monomers and small molecule peptides through electrostatic interaction and grooves to promote drug utilization. Meanwhile, tFNAs can connect miRNAs and siRNAs through specially designed sticky ends to regulate the biological functions and activities of cells. In this study, we synthesized tFNAs/Cur complexes, a novel nucleic acid drug system for promoting osteoporotic bone regeneration, to deliver Cur into BMSCs and to exert antioxidant and anti-apoptotic effects. tFNAs/Cur complexes reverse TNF-α-promoted osteogenic inhibition, and facilitate the expression of alkaline phosphatase (Alp), runt-related transcription factor 2 (Runx2), and osterix (Osx). The effect of tFNAs/Cur on the repair of tibial defects in rats with postmenopausal osteoporosis was studied. The experimental group exhibited a higher bone-formation capacity than the control group after 14 and 21 days. In conclusion, tFNAs improve Cur utilization, promote bone repair, and are promising osteoporosis-treatment interventions.