LIPOSOME-ENCAPSULATED NANOSHELLS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 水杨酸盐是阿司匹林的活性代谢物，也是用于治疗发烧、疼痛和关节炎的流行非甾体抗炎药 (NSAID) 的成员。 然而，已知它会引起溃疡，这可以通过该分子破坏覆盖胃粘膜的磷脂层的能力来解释。因为构成膜的蛋白质或脂质的化学性质的微小变化可以改变脂质膜的机械特性，并且因为静电是纳米尺度上最主要的力，所以人们相信，对水杨酸盐-脂质相互作用的更详细的测量将提供对这些基本生物过程的深入了解。 金纳米壳的表面增强拉曼散射 (SERS) 响应是由介电（二氧化硅）核和薄金属（金）壳组成的可调光学纳米颗粒，可以成为探测水杨酸盐膜相互作用的非常有用的工具。 纳米壳的光学共振在纳米颗粒表面产生强烈的光场。 纳米壳表面的高光学强度可用于增强水杨酸盐（一种拉曼活性分子）的化学光谱信号，当水杨酸盐嵌入纳米壳表面的脂质膜中时，应产生强的SERS信号。 因此，SERS 将有助于探测脂质膜特性并监测水杨酸分子插入脂质膜的情况。 插入水杨酸盐的 SERS 测量取决于纳米壳的成功脂质体封装。 这需要对脂质-纳米壳相互作用系统进行广泛的微观表征。冷冻电镜测量可以提供纳米壳脂质体封装的证据，并有助于确定纳米壳周围形成的脂质膜的厚度。因此，冷冻电镜成像对于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 的冷冻电镜设施中进行。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，纳米壳封装的脂质体还可以提供纳米壳细胞内摄取的载体，这可用于药物递送。

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.