Nontoxic Si Nanoprobes for Mulitple Biomarker Imaging

用于多种生物标志物成像的无毒硅纳米探针

• 批准号: 7361495
• 负责人: ANGELIQUE Y LOUIE
• 金额: $ 32.33万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7361495
• 关键词: Acids; Acute; Affect; Animal Model; Animals; Arterial Fatty Streak; Biodistribution; Biological; Biological Markers; Blood Clot; Blood Vessels; Blood coagulation; Cadmium; Cardiovascular system; Cell Adhesion; Cell Adhesion Molecules; Cell Culture System; Clinical; Clinical assessments; Color; Condition; Connective Tissue; Contrast Media; Coronary; Coronary Arteriosclerosis; Cultured Cells; Detection; Drug Kinetics; Evaluation; Event; Fibrin; Film; Fluorescence Microscopy; Goals; Health; Homeostasis; Human; Image; In Vitro; Inflammation; Injury; Ions; Label; Laboratory Research; Lead; Life; Magnetic Resonance; Magnetic Resonance Imaging; Methods; Modeling; Monitor; Morbidity - disease rate; Numbers; Optical Methods; Optics; Oryctolagus cuniculus; Patients; Physicians; Placement; Positron-Emission Tomography; Prevention; Preventive Medicine; Probability; Procedures; Property; Quantum Dots; Radiolabeled; Rattus; Reporting; Resolution; Risk; Route; Rupture; Semiconductors; Silicon; Solubility; Surface; System; Thrombosis; Time; Tissues; Toxic effect; Transition Elements; Vascular Diseases; Water; Week; Work; acute coronary syndrome; base; bone; cell type; clinical application; cytokine; experience; fluorescence imaging; imaging probe; in vivo; injured; interest; luminescence; macrophage scavenger receptors; mortality; nanoparticle; nanoprobe; optical imaging; quantum; radiotracer; restenosis; size; surface coating; tool; toxic metal; treatment planning; uptake

DESCRIPTION (provided by applicant): Plaque composition is an important assessment point in the prevention of acute coronary syndrome. More so than plaque size, the composition of a plaque and presence of specific markers indicate if a plaque is at risk for rupture. Rupture can lead to thrombotic events that cause mortality or morbidity. A number of plaque components have been identified that correlate with plaque stability, including cell types and cytokines associated with inflammation, but these are difficult to study in vivo. In addition, no single marker is an absolute predictor for plaque risk to rupture clinicians are increasingly interested in multiple marker assessment. Therefore a need exists for imaging methods that will allow for clinical assessment of many plaque components. Noninvasive methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are capable of imaging marker expression using targeted contrast agents, but multiple markers cannot be assessed simultaneously. If a clinician is interested to examine more than one marker, studies must be done serially, with a wait time in between for the previous targeted contrast agent to clear (for MRI), or decay (for PET). The overall goal of this proposal is to develop synthetic methods and conduct imaging studies leading toward the use of nontoxic, semiconductor, nanoparticle, imaging probes (quantum dots, QDs) in the management of human coronary artery disease. We propose to develop silicon QDs that are luminescent and also paramagnetic to allow both optical and MR imaging. Unlike traditional cadmium based QDs, silicon nanoparticles have the promise to be nontoxic as even free silicon relatively nontoxic. The QDs can be targeted to identify specific biomarkers important in cardiovascular preventative medicine and both magnetic resonance and optical imaging are then employed to assess plaque composition--MRI is used to detect regions where biomarkers are expressed, while optical methods are employed to interrogate these regions to identify the types of biomarkers present. In this proposal we describe methods to synthesize Si QDs of specific size and imaging properties, characterize the toxicity and uptake of these nanoparticles in cell cultures, and demonstrate the utility for these QDs to label multiple biomarkers of plaque stability in an animal model. The proposed work develops a new imaging material that would allow physicians to assess whether an arterial plaque was at risk to rupture. Plaque rupture is a graver threat to health than the size of the plaque. The physician can use this information to decide on treatment plans for the patient and to identify plaques that need to be more carefully monitored.

描述（由申请人提供）：斑块组成是预防急性冠状动脉综合征的重要评估点。比斑块大小更重要的是，斑块的组成和特定标记的存在表明牙菌斑是否有破裂的风险。破裂会导致导致死亡率或发病率的血小板事件。已经鉴定出许多与斑块稳定性相关的斑块成分，包括与炎症相关的细胞类型和细胞因子，但这些因子很难在体内研究。此外，没有单个标记是破裂临床医生斑块风险的绝对预测因子，对多个标记评估越来越感兴趣。因此，需要对成像方法的需求，该方法将允许对许多斑块成分进行临床评估。诸如磁共振成像（MRI）和正电子发射断层扫描（PET）之类的非侵入性方法能够使用靶向对比剂对标记表达进行成像表达，但是不能同时评估多个标记。如果临床医生有兴趣检查多个标记物，则必须连续进行研究，以便在以前的靶向对比剂清除（用于MRI）或衰减（用于PET）之间的等待时间。该提案的总体目标是开发合成方法并进行成像研究，导致在人类冠状动脉疾病的管理中使用无毒，半导体，纳米颗粒，成像探针（量子点，QD）。我们建议开发发光且磁磁很发光的硅QD，以允许光学成像和MR成像。与传统的基于镉的QD不同，硅纳米颗粒具有无毒的硅纳米颗粒，即使是自由硅相对较无毒。可以将QD靶向识别在心血管预防医学中重要的特定生物标志物，然后使用磁共振和光学成像来评估斑块组成 - MRI- MRI用于检测表达生物标记物的区域，而光学方法则采用光学方法来审查这些区域，以识别存在类型的生物标志物。在此提案中，我们描述了合成特定大小和成像特性的SI QD的方法，表征了这些纳米颗粒在细胞培养物中的毒性和摄取，并证明了这些QD的效用，以标记动物模型中斑块稳定性的多个生物标志物。拟议的工作开发了一种新的成像材料，该材料将使医生能够评估动脉斑块是否有破裂的风险。牙菌斑破裂是对健康的严重威胁，而不是斑块的大小。医师可以使用这些信息来决定患者的治疗计划，并确定需要更仔细监测的斑块。