LIPOSOME-ENCAPSULATED NANOSHELLS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 研究中心，而研究中心不一定是研究者所在的机构。 水杨酸盐是阿司匹林的活性代谢产物，也是用于治疗发热、疼痛和关节炎的常用非甾体抗炎药（NSAID）的一员。 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。由于脂质膜的机械性质可以通过组成膜的蛋白质或脂质的化学性质的微小变化而改变，并且由于静电是纳米级的最主要的力，因此相信水杨酸酯-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见解。 金纳米壳是由介电（二氧化硅）核和薄金属（金）壳组成的可调光学纳米颗粒，其表面增强拉曼散射（Sers）响应可以是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的表面产生强烈的光场。 纳米壳表面的高光强可用于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，当其嵌入纳米壳表面的脂质膜中时，应产生强Sers信号。 因此，Sers将是有用的探测脂质膜的性质和监测水杨酸分子插入到脂质膜。 插入的水杨酸酯的Sers测量取决于成功的纳米壳的脂质体包封。 这需要对脂质-纳米壳相互作用系统进行广泛的微观表征。CryoEM测量可以提供纳米壳的脂质体包封的证据，并且可以帮助建立在纳米壳周围形成的脂质膜的厚度。因此，cryoEM成像对于该项目的进展至关重要。 将在NCMI的cryoEM机构对制备的脂质体-纳米壳样品进行成像。从我们的研究结果将我们的连续微观力学测量分子相互作用。 除了研究水杨酸盐对膜动力学的影响之外，纳米壳封装的脂质体可以提供用于细胞内摄取纳米壳的媒介物，其可以用于药物递送。

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.