使用间充质干细胞靶向3WJ纳米颗粒和报道的特异性递送抗mirna 138治疗骨质疏松症

IF 4.3 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

ACS Omega Pub Date : 2025-03-04 eCollection Date: 2025-03-18 DOI:10.1021/acsomega.4c11505

Liangliang Xu, Xiangzhong Liu, Jian Chen, Liwei Xu, Aofei Yang, Zhanghua Li

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引用次数: 0

摘要

目的：锁定核酸（LNA）修饰的抗microrna已被证明可靶向间充质干细胞（MSCs）治疗骨病。但其“脱靶”效应限制了其临床应用。方法：选择MSCs特异性适配体M4，以三向结（3WJ）为核心支架构建抗mirna 138特异性递送纳米颗粒（3WJ-M4- lna）。结果：我们的研究结果表明，3WJ-M4- lna纳米颗粒，而不是3WJ-M4或3WJ-LNA，可以特异性地向MSCs传递抗miRNA，从而显著抑制miRNA 138的表达。我们的实验进一步证实了纳米颗粒通过激活ERK1/2通路促进MSCs的成骨分化。在兔骨质疏松模型中，纳米颗粒促进骨形成，改善骨微结构。结论：这些结果表明3WJ纳米颗粒可能成为骨质疏松症的特异性治疗策略。

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Use of Mesenchymal Stem Cell-Targeting 3WJ Nanoparticles and Reported Specific Delivery of Anti-miRNA 138 to Treat Osteoporosis.

Purpose: Locked nucleic acid (LNA)-modified anti-microRNAs have been demonstrated to target mesenchymal stem cells (MSCs) to treat bone diseases. However, the "off-target" effect limits its clinical application.

Methods: We selected specific aptamer M4 of MSCs and employed the three-way junction (3WJ) as the core scaffold to construct nanoparticles (3WJ-M4-LNA) for specific delivery of anti-miRNA 138.

Results: Our results suggested that the 3WJ-M4-LNA nanoparticles, not 3WJ-M4 or 3WJ-LNA, can specifically deliver anti-miRNA to MSCs, resulting in significant inhibition of miRNA 138 expression. Our experiment further confirmed that the nanoparticles can promote MSCs' osteogenic differentiation by activating the ERK1/2 pathway. In vivo, the nanoparticles promoted bone formation and improved the bone microarchitecture in rabbit osteoporosis models.

Conclusions: These results indicate that the 3WJ nanoparticles could develop as a specific therapeutic strategy for osteoporosis.

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来源期刊

ACS Omega Chemical Engineering-General Chemical Engineering

CiteScore

6.60

自引率

4.90%

发文量

3945

审稿时长

2.4 months

期刊介绍： ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.