Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
Nanoscale. 2017 Mar 9;9(10):3408-3415. doi: 10.1039/c6nr06948g.
Nanoparticles offer great potential in drug delivery and imaging, but shielding strategies are necessary to increase circulation time and performance. Structure-function studies are required to define the design rules to achieve effective shielding. With several formulations reaching clinical testing and approval, the ability to assess and detail nanoparticle formulations at the single particle level is becoming increasingly important. To address this need, we use cryo-electron tomography (cryo-ET) to investigate stealth-coated nanoparticles. As a model system, we studied the soft matter nanotubes formed by tobacco mosaic virus (TMV) coated with human serum albumin (SA) stealth proteins. Cryo-ET and subtomogram averaging allow for visualization of individual SA molecules and determination of their orientations relative to the TMV surface, and also for measurement of the surface coverage provided by added stealth proteins. This information fills a critical gap in the understanding of the structural morphology of stealth-coated nanoparticles, and therefore cryo-ET may play an important role in guiding the development of future nanoparticle-based therapeutics.
纳米粒子在药物输送和成像方面具有巨大的潜力，但需要屏蔽策略来增加循环时间和性能。需要进行结构-功能研究，以确定实现有效屏蔽的设计规则。随着几种制剂进入临床测试和批准，评估和详细描述纳米粒子制剂在单个粒子水平上的能力变得越来越重要。为了满足这一需求，我们使用冷冻电子断层扫描（cryo-ET）来研究隐形涂层纳米粒子。作为一个模型系统，我们研究了烟草花叶病毒（TMV）涂覆人血清白蛋白（SA）隐形蛋白形成的软物质纳米管。冷冻电子断层扫描和亚断层平均允许可视化单个 SA 分子，并确定它们相对于 TMV 表面的取向，还可以测量添加隐形蛋白提供的表面覆盖率。这些信息填补了对隐形涂层纳米粒子结构形态理解的关键空白，因此冷冻电子断层扫描可能在指导未来基于纳米粒子的治疗药物的开发中发挥重要作用。
