Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment of hindlimb ischemia.

Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment of hindlimb ischemia.
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DOI:
10.1038/srep03883
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发表时间:
2014-01-24
期刊:
影响因子:
4.6
通讯作者:
Aramaki Y
Aramaki Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Endo-Takahashi Y;Negishi Y;Nakamura A;Ukai S;Ooaku K;Oda Y;Sugimoto K;Moriyasu F;Takagi N;Suzuki R;Maruyama K;Aramaki Y

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目前,微RNA (miRNA)被认为是治疗干预的一个有吸引力的靶点。基于miRNA的治疗的一个重要障碍是miRNA有效地递送到目标组织。我们开发了聚乙二醇修饰脂质体(气泡脂质体(BLs)),它可以捕获超声造影剂气体,可以作为质粒DNA (pDNA)或小干扰RNA (siRNA)载体和超声造影剂。在这项研究中,我们使用后肢缺血模型和miR-126来研究装载mirna的BLs (mi-BLs)的可用性。据报道,miR-126通过抑制VEGF信号的负调节因子来促进血管生成。我们证明了使用诊断性US可以检测到mi-BLs,并且使用治疗性US的mi-BLs可以将miR-126传递到缺血后肢,从而诱导血管生成因子并改善血流。这些结果表明,将mi-BLs与US结合可能有助于US成像和miRNA传递。
Currently, micro RNA (miRNA) is considered an attractive target for therapeutic intervention. A significant obstacle to the miRNA-based treatments is the efficient delivery of miRNA to the target tissue. We have developed polyethylene glycol-modified liposomes (Bubble liposomes (BLs)) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA (pDNA) or small interfering RNA (siRNA) carriers and US contrast agents. In this study, we investigated the usability of miRNA-loaded BLs (mi-BLs) using a hindlimb ischemia model and miR-126. It has been reported that miR-126 promotes angiogenesis via the inhibition of negative regulators of VEGF signaling. We demonstrated that mi-BLs could be detected using diagnostic US and that mi-BLs with therapeutic US could deliver miR-126 to an ischemic hindlimb, leading to the induction of angiogenic factors and the improvement of blood flow. These results suggest that combining mi-BLs with US may be useful for US imaging and miRNA delivery.
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