Platelet membrane-cloaked nanoparticles for targeting and imaging of atherosclerosis

项目摘要 背景：动脉粥样硬化是一种无症状的疾病，可以进展到非常晚期， 明显的症状;准确和快速地检测它对它的管理至关重要。电流 用于动脉粥样硬化的成像技术通常是非靶向的或缺乏分辨率或信噪比 这是准确检测所必需的。即使是最先进的用于成像的靶向颗粒通常也依赖于 在它们的表面上只有单一的靶向部分。我们的设计是一种血小板膜包裹的纳米颗粒， 一种具有多种途径结合动脉粥样硬化部位的物质， 面向.血小板自然有一个密切的关系，发展斑块在发炎 内皮部位，并加速动脉粥样硬化的进展。我们可以利用这个 自然属性，以设计具有血小板固有特性的载体，这将阐明 对动脉粥样硬化部位具有高度的特异性和敏感性。 目的： 目的1：在体外和离体测试PNPs与动脉粥样硬化的各种指标的结合。 目的2：评价使用染料负载的PNP在体内检测动脉粥样硬化区域。 目的3：研究PNP作为临床显像剂的翻译能力，使用氧化铁血小板 膜包被的纳米颗粒。 结论：前两个目的将证实血小板膜表面，与所有的受体 并且完整的并包被在颗粒表面上的整联蛋白将靶向并结合动脉粥样硬化部位。 第三个目标将确认该平台可以通过临床相关性用于人类。 用片状膜包覆氧化铁纳米颗粒。我们的假设是，通过利用 存在于活化血小板表面的天然生物分子和受体， 纳米颗粒的表面，我们可以设计多价结合的造影剂颗粒。这是一 临床相关系统，可帮助心血管疾病患者进行MR成像。

Project Summary Background: Atherosclerosis is a silent disease which can progress to very late stages without highly noticeable symptoms; detecting it accurately and quickly is paramount to its management. Current imaging techniques for atherosclerosis are often untargeted or lack the resolution or signal to noise ratio necessary for accurate detection. Even state-of-the-art targeted particles for imaging typically rely on only a single targeting moiety on their surface. Our design is a platelet membrane-coated nanoparticle, a material which has multiple pathways for binding to atherosclerotic sites, and would give multiplex targeting. Platelets naturally have an intimate relationship with the development of plaque at inflamed endothelium sites, and quicken the progression of atherosclerosis. We can take advantage of this natural property to design carriers with the intrinsic properties of platelets, which will illuminate atherosclerotic sites at high specificity and sensitivity. Aims: Aim 1: Test binding of PNPs to various indicators of atherosclerosis in vitro and ex vivo. Aim 2: Evaluate the detection of atherosclerotic regions in vivo using dye loaded PNPs. Aim 3: Investigate translational ability of PNPs as a clinical imaging agent using iron oxide platelet membrane-coated nanoparticles. Conclusion: The first two aims will verify that the surface of platelet membrane, with all the receptors and integrins intact, and coated onto the surface of particles, will target and bind to atherosclerotic sites. The third aim will confirm that this platform can be made clinically relevant for use in humans by the coating of an iron oxide nanoparticle with platelet membrane. Our hypothesis is that by utilizing the natural biomolecules and receptors present on the surface of activated platelets, and coating them onto the surface of nanoparticles, we can design multivalently-binding contrast agent particles. This is a clinically relevant system which could aid MR imaging in patients with cardiovascular disease.