LIPOSOME-ENCAPSULATED NANOSHELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 水杨酸盐是阿司匹林的活性代谢物，是治疗发烧、疼痛和关节炎的常用非类固醇抗炎药(NSAIDs)的一员。然而，已知会导致溃疡，这可以通过分子破坏覆盖在胃粘膜上的磷脂层的能力来解释。由于脂膜的机械性能可以通过组成膜的蛋白质或脂类的化学成分的微小变化来改变，而且静电是纳米尺度上最主要的作用力，因此人们相信，对水杨酸盐-脂类相互作用的更详细测量将提供对这些基本生物过程的洞察。 金纳米壳是由介电(二氧化硅)核和薄金属(金)壳组成的可调谐光学纳米粒子，其表面增强拉曼散射(SERS)响应是探测水杨酸膜相互作用的非常有用的工具。纳米壳层的光学共振在纳米颗粒表面产生了强烈的光场。纳米壳表面的高光强可以用来增强水杨酸盐的化学光谱信号，水杨酸盐是一种拉曼活性分子，当嵌入到纳米壳表面的脂膜中时，应该会产生强烈的SERS信号。因此，表面增强拉曼光谱将有助于探测脂膜的性质和监测水杨酸分子插入脂膜。插入水杨酸盐铰链的表面增强拉曼光谱测量取决于脂质体成功包裹纳米壳。这需要对脂质-纳米壳相互作用系统进行广泛的微观表征。低温电子显微镜测量可以提供纳米壳被脂质体包裹的证据，并有助于确定纳米壳周围形成的脂膜的厚度。因此，低温电磁成像对该项目的进展至关重要。制备的脂质体-纳米壳样品的成像将在NCMI的CryoEM设施进行。我们的研究结果将把我们的连续微机械测量与分子相互作用联系起来。除了研究水杨酸盐对膜动力学的影响外，纳米壳包裹的脂质体还可以提供一种在细胞内摄取纳米壳的载体，这可能有助于药物的输送。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Salicylate is the active metabolite of aspirin and a member of the popular non-steroidal anti-inflammatory drugs (NSAIDs) used to treat fever, pain and arthritis. However, it is known to cause ulcers, which could be explained by the ability of the molecule to disrupt the phospholipid layer covering the gastric mucosa. Because mechanical properties of a lipid membrane can be altered by minor changes in the chemistry of the proteins or lipids that compose the membrane, and because electrostatics is the most dominant force at the nanoscale, it is believed that more detailed measurements of salicylate-lipid interactions will provide insights into these fundamental biological processes. Surface-Enhanced Raman Scattering (SERS) response of gold nanoshells, which are tunable optical nanoparticles consisting of a dielectric (silica) core and a thin metallic (gold) shell, can be a very useful tool to probe salicylate membrane interactions. The optical resonance of nanoshells gives rise to an intense optical field at the surface of the nanoparticle. The high optical intensities at the nanoshell surface can be used to enhance the chemical spectroscopic signal of salicylate, a Raman-active molecule, which when embedded in a lipid membrane on the surface of the nanoshell should yield a strong SERS signal. Thus, SERS will be useful to probe lipid membrane properties and monitor the insertion of salicylic acid molecules into the lipid membrane. SERS measurements of inserted salicylate hinges on successful liposome- encapsulation of nanoshells. This requires extensive microscopic characterization of the lipid-nanoshell interacting system. CryoEM measurements can provide evidence of liposome-encapsulation of nanoshells and can help establish the thickness of the lipid membrane formed around the nanoshells. Therefore, cryoEM imaging is essential to the progress of this project. Imaging of the prepared liposome-nanoshell samples will be conducted at the cryoEM facility at NCMI. Results from our studies will relate our continuum micromechanical measurements to molecular interactions. In addition to studying the effect salicylate has on membrane dynamics, nanoshell-encapsulated liposomes may provide a vehicle for intracellular uptake of nanoshells which can be useful for drug delivery.