LIPOSOME-ENCAPSULATED NANOSHELLS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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，也是常用的非甾体抗炎药（NSAIDs）的一种，用于治疗发烧、疼痛和关节炎。然而，已知它会引起溃疡，这可以通过分子破坏覆盖胃粘膜的磷脂层的能力来解释。由于组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，并且由于静电是纳米尺度上最主要的力，因此人们相信对水杨酸-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）壳组成的可调谐光学纳米粒子，它的表面增强拉曼散射（SERS）响应是探测水杨酸盐膜相互作用的一个非常有用的工具。纳米壳的光学共振在纳米粒子表面产生强烈的光场。纳米壳表面的高光强可以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，当水杨酸盐嵌入纳米壳表面的脂质膜时，会产生强的SERS信号。因此，SERS将有助于探测脂质膜的性质，并监测水杨酸分子进入脂质膜的情况。插入水杨酸盐的SERS测量取决于纳米壳的脂质体包封成功。这需要对脂质-纳米壳相互作用系统进行广泛的微观表征。低温电镜测量可以提供纳米壳脂质体包封的证据，并可以帮助确定纳米壳周围形成的脂膜的厚度。因此，低温电镜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的低温电子显微镜设备上进行。我们的研究结果将把我们的连续微力学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，纳米壳包封脂质体可能为细胞内摄取纳米壳提供一种载体，这对药物递送很有用。

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.