A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy.
A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy.
复制标题
一种骨吸收表面靶向纳米颗粒，可提供抗 miR214 用于骨质疏松症治疗
DOI：
10.2147/ijn.s139775
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发表时间：
2017
影响因子：
8
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Cai M;Yang L;Zhang S;Liu J;Sun Y;Wang X
随着脆性骨折风险的增加，骨质疏松症是威胁绝经后妇女的全球性健康问题。在这些患者中，破骨细胞在骨丢失和骨折中起主导作用。如何抑制破骨细胞活性是骨质疏松症治疗的关键问题。近年来，基于miRNA的基因治疗通过基因调控被认为是一种有潜力的治疗方法。然而，考虑到副作用，治疗性miRNAs在骨质疏松症治疗中的应用仍然受到缺乏组织/细胞特异性递送系统的限制。在这里，我们开发了酸性多肽Asp8修饰的聚氨酯(PU)纳米胶束。我们的数据显示，这种传递系统在体内将miRNAs包裹并选择性地传递给骨吸收表面的OSCAR+破骨细胞，没有明显的毒性或引发免疫反应。通过Asp8-PU给药系统，将抗miR214基因导入破骨细胞，改善了去卵巢骨质疏松小鼠的骨微结构和骨量。因此，ASP8-PU可作为骨吸收表面靶向给药系统，用于治疗破骨细胞引起的骨病和老年性骨质疏松。
With increasing fracture risks due to fragility, osteoporosis is a global health problem threatening postmenopausal women. In these patients, osteoclasts play leading roles in bone loss and fracture. How to inhibit osteoclast activity is the key issue for osteoporosis treatment. In recent years, miRNA-based gene therapy through gene regulation has been considered a potential therapeutic method. However, in light of the side effects, the use of therapeutic miRNAs in osteoporosis treatment is still limited by the lack of tissue/cell-specific delivery systems. Here, we developed polyurethane (PU) nanomicelles modified by the acidic peptide Asp8. Our data showed that without overt toxicity or eliciting an immune response, this delivery system encapsulated and selectively deliver miRNAs to OSCAR+ osteoclasts at bone-resorption surface in vivo. With the Asp8-PU delivery system, anti-miR214 was delivered to osteoclasts, and bone microarchitecture and bone mass were improved in ovariectomized osteoporosis mice. Therefore, Asp8-PU could be a useful bone-resorption surface-targeting delivery system for treatment of osteoclast-induced bone diseases and aging-related osteoporosis.