Novel angiogenic therapy using siRNA-loaded Bubble liposomes with ultrasound exposure

最近，我们开发了聚乙二醇改性的脂质体(气泡脂质体；BLS)，包裹了超声(US)成像气体。在本研究中，我们利用阳离子脂类、DOTAP、DSTAP、DSDAP和DDAB制备了新型的siRNA负载BLS(si-BLS)，并考察了这些BLS作为载体和US造影剂的可用性。我们证明了siRNA可以负载到BLS上，并且负载siRNA的BLS在血清中是稳定的。通过si-BLS的转染，也获得了特异性的基因沉默效应。我们还可以从超声成像、基因转移效率和毒性方面对BLS的脂质成分进行优化。此外，尾静脉注射BLS可达到模型小鼠缺血后肢。这些结果表明，该方法可能成为血管生成治疗的有用工具。

Recently, we developed polyethyleneglycol(PEG)-modified liposomes(Bubble liposomes ; BLs) entrapping an ultrasound(US) imaging gas. In this study, we prepared novel siRNA-loaded BLs(si-BLs) using cationic lipids, DOTAP, DSTAP, DSDAP, and DDAB, and examined the usability of those BLs as a carrier and an US contrast agent. We demonstrated that siRNA could be loaded onto BLs and that siRNA-loaded BLs was stable in serum. A specific gene-silencing effect was also achieved by transfection with si-BLs. We also could optimize the lipid component of BLs in terms of the US imaging, the gene transfer efficiency, and toxicity. Furthermore, BLs injected into tail vein could reached to ischemic hindlimb of model mice. These results suggest that this method could be a useful tool for angiogenic therapy.