Active loading of cyanine 5.5 derivatives into liposomes for deep self-quenching and their applications in deep tissue imaging†

IF 3.5 Q2 CHEMISTRY, ANALYTICAL
Chong-Yan Chen, Cheng-Bang Jian, Hua-De Gao, Xu-En Yu, Yuan-Chih Chang, Shwee Khuan Leong, Jiun-Jie Shie and Hsien-Ming Lee
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Abstract

Visualizing liposome release profiles in small animals is important for evaluating the pharmacokinetic influence of vesicles. Encapsulating near-infrared (NIR) fluorescent dyes to visualize and report liposomal cargo release in vivo, which necessitates high encapsulation with deep self-quenching, is highly desirable in advanced (such as targeting or trigger-release) liposome development. However, passive loading of NIR dyes usually yields low encapsulation efficiencies (1–5%), causing significant wastage and cost-ineffectiveness while using expensive NIR fluorescent dyes. It would be highly beneficial if an active loading method, which typically has an encapsulation efficiency of nearly 100%, is developed. This research describes an active loading approach for two cyanine 5.5 (Cy5.5) derivatives. We discovered that using ammonium sucrose octasulfate (ASO) as a trapping agent allows for nearly 100% encapsulation for both Cy5.5 dyes, accompanied by the formation of nanoprecipitates inside the liposome, as evidenced by cryogenic electron microscopy. Fluorescence spectroscopy confirmed deep fluorescence self-quenching after active loading and a 60–100-fold fluorescence enhancement upon full content release via liposome rupture. Cellular uptake experiments showed that the fluorescence of Cy5.5-loaded liposomes recovered and plateaued after 9 hours of incubation with cells. In vivo fluorescence imaging (IVIS) demonstrated the same fluorescence activation in tumor-bearing mice intratumorally injected with the liposome. We believe that the developed active loading method will enable Cy5.5-loaded liposomes to be a deep tissue-compatible and cost-effective NIR fluorescence release-reporting platform.

Abstract Image

具有深度自淬灭特性的活性负载脂质体蓝 5.5 衍生物及其在深部组织成像中的应用
观察脂质体在小动物体内的释放情况对于评估囊泡的药代动力学影响非常重要。封装近红外(NIR)荧光染料以可视化和报告脂质体货物在体内的释放情况,需要高封装度和深度自淬火,这在高级(如靶向或触发释放)脂质体开发中是非常理想的。然而,被动装载的近红外染料通常封装效率较低(1-5%),导致大量浪费,并且在使用昂贵的近红外荧光染料时存在成本效益不高的问题。如果能开发出通常封装效率接近 100%的主动装载方法,将大有裨益。本研究介绍了两种 5.5(Cy5.5)氰衍生物的活性负载方法。我们发现,使用蔗糖八硫酸铵(ASO)作为捕获剂,可使两种 Cy5.5 染料的封装率接近 100%,同时还能在脂质体内部形成纳米沉淀物,这一点已被低温电子显微镜所证实。荧光光谱分析证实,活性负载后会产生深度荧光自淬,脂质体破裂后,其内容物完全释放,荧光增强 60-100 倍。细胞吸收实验表明,Cy5.5负载脂质体的荧光在与细胞培养9小时后恢复并趋于平稳。体内荧光成像(IVIS)显示,肿瘤小鼠瘤内注射脂质体后,荧光同样被激活。我们相信,所开发的活性负载方法将使 Cy5.5 负载脂质体成为一种深层组织兼容且经济高效的近红外荧光释放报告平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
2.30
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