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静止性疾病，可以进展到非常晚期，而不是高度 明显的症状；准确和快速地检测对其管理至关重要。当前 动脉粥样硬化的成像技术通常没有针对性，或者缺乏分辨率或信噪比 对于准确的检测是必要的。即使是最先进的靶向成像粒子通常也依赖于 在它们的表面上只有一个目标部分。我们的设计是一种血小板膜包裹的纳米颗粒， 一种具有与动脉粥样硬化部位结合的多个途径的材料，并将产生多个 瞄准目标。血小板自然与炎症时斑块的形成有密切关系 血管内皮细胞定位，加速动脉粥样硬化的进展。我们可以利用这一点 将天然属性设计为具有血小板固有属性的载体，这将说明 动脉粥样硬化部位具有较高的特异性和敏感性。 目标： 目的1：检测PNPs与各种动脉粥样硬化指标的体外结合情况。 目的2：评价染料负载PNPs在体内检测动脉粥样硬化区的效果。 目的3：研究PNPs作为临床显像剂的翻译能力 薄膜包裹的纳米颗粒。 结论：前两个目的将验证血小板膜表面与所有受体 而完整的整合素，并被包裹在颗粒表面，将靶向并结合到动脉粥样硬化部位。 第三个目标将确认该平台可以通过在临床上相关的人类使用 用血小板膜包覆纳米氧化铁。我们的假设是，通过利用 天然生物分子和受体存在于激活的血小板表面，并将它们涂覆在 在纳米颗粒的表面，我们可以设计多价结合的造影剂颗粒。这是一个 临床相关系统，可帮助心血管疾病患者进行磁共振成像。

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.