Integrated Nanosystems for Diagnosis and Therapy

用于诊断和治疗的集成纳米系统

• 批准号: 7231462
• 负责人: Karen L. Wooley
• 金额: $ 264.19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231462
• 关键词: Integrated; Nanosystems; Diagnosis; Therapy

DESCRIPTION (provided by applicant): A multidisciplinary team of scientists, nanotechnologists and physicians will establish a Program of Excellence in Nanotechnology (PEN), with the central focus being research and educational activities related to "Integrated Nanosystems for Diagnosis and Therapy". This PEN will include investigators from the Schools of Arts & Sciences and Medicine at Washington University, as well as nanotechnologists from the University of California campuses at Berkeley and Santa Barbara. The central mission is the development of a group of well-characterized and versatile nanoscale agents that can be assembled, labeled, targeted, filled, and activated as needed for the combined purposes of diagnosis and treatment of various diseases of relevance to NHLBI. The overall experimental strategy will focus on biological models of acute pulmonary and systemic vascular Injury (in vitro and in vivo) to demonstrate the effectiveness of these agents. There are six specific aims for this PEN: (1) Preparation and assembly of programmed, integrated nanosystems; (2) Application of nanostructures for imaging at increased levels of sensitivity; (3) Imaging of gene expression by recognition of mRNA transcription products; (4) Application of the nanostructures for therapy; (5) Cross disciplinary education and training of medical and materials scientists, and; (6) Dissemination and translation of nanotechnology developments. Fundamental studies will be conducted to understand the potential roles and limitations for nanotechnology as applied to medicine, and a number of applied studies will work toward the implementation of well-defined nanostructures for diagnosis and treatment of acute vascular injury and inflammation, with validation in the lung and cardio-vasculature. General methodologies will be developed for the preparation and characterization of novel plurifunctional nanostructures that can serve as hosts for both diagnostic and therapeutic agents, and then be destroyed safely once they have fulfilled their function (Aim 1). Demonstration of enhanced imaging capabilities will be performed for radio-, MR- and optically-labeled nanostructures by positron emission tomography, magnetic resonance and optical imaging, respectively, whereby tissues are targeted via ligands for cell surface receptors (Aim 2). Intracellular targeting will also be developed to allow for identification and "reading" of mRNA, as a means to perform direct Imaging of gene products that are either unregulated in a disease state or that are the products of gene transfer (Aim 3). It is expected that these new approaches will be applicable generally as a new form of molecular imaging that eliminates the need for reporter genes. In addition to the imaging of acute vascular injury, treatment by the delivery of various therapeutic agents using an array of nanoscale materials will be developed (Aim 4). Critical to the success of this PEN will be the establishment of infrastructure for the education, training and mentoring of students and postdoctorals, through formal course, workshops and laboratory rotations (Aim 5), and to the establishment of an affective and broadly based mechanism for dissemination of results, procedures and programs (Aim 6). Through these initiatives, we will provide leadership for the development of nanoscience and nanotechnology that can impact clinical directives and capabilities through the 21st century.

描述（由申请人提供）： 由科学家，纳米技术医生和医生组成的多学科团队将建立纳米技术卓越的卓越计划（PEN），中心重点是与“综合纳米系统进行诊断和治疗”有关的研究和教育活动。这支笔将包括华盛顿大学艺术与科学与医学学院的调查人员，以及来自伯克利分校和圣塔芭芭拉大学校园的纳米技术学家。中心任务是开发一组特征良好的多功能纳米级药物，可以根据需要组装，标记，靶向，填充和激活，以诊断和治疗与NHLBI相关性的各种疾病。总体实验策略将集中于急性肺和全身血管损伤的生物学模型（体外和体内），以证明这些药物的有效性。这支笔有六个具体的目标：（1）编程，集成的纳米系统的准备和组装； （2）纳米结构在提高灵敏度水平下的成像； （3）通过识别mRNA转录产物对基因表达的成像； （4）应用纳米结构进行治疗； （5）跨学科教育和医学和材料科学家的培训，以及； （6）纳米技术发展的传播和翻译。将进行基本研究，以了解适用于医学的纳米技术的潜在作用和局限性，许多应用研究将致力于实施明确定义的纳米结构，以诊断和治疗急性血管损伤和炎症，并在肺和心脏血管中进行验证。将开发一般的方法论，用于制备和表征新型的多功能纳米结构，这些纳米结构可以作为诊断和治疗剂的宿主，然后一旦履行其功能就可以安全地破坏（AIM 1）。将分别通过正电子发射断层扫描，磁共振和光学成像来为射，MR和光学标记的纳米结构进行增强的成像能力演示，从而通过配体来针对细胞表面受体（AIM 2）。还将开发细胞内靶向，以允许对mRNA的识别和“读取”，以作为对在疾病状态下不受监管的基因产物进行直接成像的手段，或者是基因转移的产物（AIM 3）。预计这些新方法将通常作为一种新形式的分子成像形式，从而消除了对报告基因的需求。除了对急性血管损伤的成像外，还将开发使用各种纳米级材料的各种治疗剂治疗（AIM 4）。这笔笔的成功至关重要的是建立通过正式课程，讲习班和实验室轮换（AIM 5）以及建立一种情感和广泛的基于情感和广泛的机制来建立教育，培训和指导学生和博士后的教育，培训和指导，以传播结果，程序和计划（AIM 6）。通过这些举措，我们将为纳米科学和纳米技术的发展提供领导，这些纳米科学和纳米技术可以影响21世纪的临床指示和能力。