Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery
Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery
复制标题
用于 siRNA/microRNA 递送的成骨细胞靶向肽修饰纳米颗粒
DOI：
10.1021/acsnano.5b07828
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发表时间：
2016-06-01
期刊：
影响因子：
17.1
通讯作者：
Wang, Xiaogang
中科院分区：
文献类型：
--
作者：
Sun, Yao;Ye, Xiongzhen;Wang, Xiaogang
抗骨质疏松基因药物的开发策略目前集中在靶向成骨细胞，以抑制骨丢失或增加骨量。尽管基于siRNA/microRNA的基因治疗具有巨大的潜力，但由于缺乏特异性细胞靶向递送系统，其受到严重限制。我们报告了一种成骨细胞靶向肽（SDSSD），它通过骨膜蛋白选择性地与成骨细胞结合。我们开发了SDSSD改性的聚氨酯（PU）纳米胶束，封装siRNA/microRNA，将药物递送到成骨细胞;数据显示，SDSSD PU不仅可以选择性靶向骨形成表面，还可以靶向成骨细胞，而不会产生明显的毒性或引发体内免疫反应。我们使用SDSSD PU递送系统将抗miR-214递送至成骨细胞，并且我们的结果显示在卵巢切除骨质疏松症小鼠模型中骨形成增加、骨微结构改善和骨量增加。SDSSD PU可能是一种有用的成骨细胞靶向小核酸递送系统，可用作治疗成骨细胞诱导的骨疾病的合成代谢策略。
Antiosteoporosis gene-based drug development strategies are presently focused on targeting osteoblasts to either suppress bone loss or increase bone mass. Although siRNA/microRNA-based gene therapy has enormous potential, it is severely limited by the lack of specific cell targeting delivery systems. We report an osteoblast-targeting peptide (SDSSD) that selectively binds to osteoblasts via periostin. We developed SDSSD-modified polyurethane (PU) nanomicelles encapsulating siRNA/microRNA that delivers drugs to osteoblasts; the data showed that SDSSD PU could selectively target not only bone-formation surfaces but also osteoblasts without overt toxicity or eliciting an immune response in vivo. We used the SDSSD PU delivery system to deliver anti-miR-214 to osteoblasts and our results showed increased bone formation, improved bone microarchitecture, and increased bone mass in an ovariectomized osteoporosis mouse model. SDSSD PU may be a useful osteoblast-targeting small nucleic acid delivery system that could be used as an anabolic strategy to treat osteoblast-induced bone diseases.