Oda Yusuke, Suzuki Ryo, Mori Tatsuya, Takahashi Hideyo, Natsugari Hideaki, Omata Daiki, Unga Johan, Uruga Hitoshi, Sugii Mutsumi, Kawakami Shigeru, Higuchi Yuriko, Yamashita Fumiyoshi, Hashida Mitsuru, Maruyama Kazuo
Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
Laboratory of Organic Chemistry, Faculty of Pharma-Sciences, Teikyo University, Japan.
Int J Pharm. 2015 Jun 20;487(1-2):64-71. doi: 10.1016/j.ijpharm.2015.03.073. Epub 2015 Apr 1.
Nano-/microbubbles are expected not only to function as ultrasound contrast agents but also as ultrasound-triggered enhancers in gene and drug delivery. Notably, nanobubbles have the ability to pass through tumor vasculature and achieve passive tumor targeting. Thus, nanobubbles would be an attractive tool for use as ultrasound-mediated cancer theranostics. However, the amounts of gas carried by nanobubbles are generally lower than those carried by microbubbles because nanobubbles have inherently smaller volumes. In order to reduce the injection volume and to increase echogenicity, it is important to develop nanobubbles with higher gas content. In this study, we prepared 5 kinds of fluoro-lipids and used these reagents as surfactants to generate "Bubble liposomes", that is, liposomes that encapsulate nanobubbles such that the lipids serve as stabilizers between the fluorous gas and water phases. Bubble liposome containing 1-stearoyl-2-(18,18-difluoro)stearoyl-sn-glycero-3-phosphocholine carried 2-fold higher amounts of C3F8 compared to unmodified Bubble liposome. The modified Bubble liposome also exhibited increased echogenicity by ultrasonography. These results demonstrated that the inclusion of fluoro-lipid is a promising tool for generating nanobubbles with increased efficiency of fluorous gas carrier.
纳米/微泡不仅有望用作超声造影剂,还能作为基因和药物递送中超声触发的增强剂。值得注意的是,纳米气泡有能力穿过肿瘤血管并实现被动肿瘤靶向。因此,纳米气泡将是一种有吸引力的工具,可用作超声介导的癌症诊疗手段。然而,纳米气泡携带的气体量通常低于微气泡,因为纳米气泡本身的体积较小。为了减少注射体积并提高回声性,开发具有更高气体含量的纳米气泡很重要。在本研究中,我们制备了5种氟脂质,并使用这些试剂作为表面活性剂来生成“气泡脂质体”,即包裹纳米气泡的脂质体,使得脂质在氟代气体和水相之间起到稳定剂的作用。与未修饰的气泡脂质体相比,含有1-硬脂酰-2-(18,18-二氟)硬脂酰-sn-甘油-3-磷酸胆碱的气泡脂质体携带的C3F8量高出2倍。经修饰的气泡脂质体在超声检查中也表现出增强的回声性。这些结果表明,包含氟脂质是一种有前景的工具,可用于生成具有更高效率的氟代气体载体的纳米气泡。