Integrated Nanosystems for Diagnosis and Therapy

用于诊断和治疗的集成纳米系统

• 批准号: 7623131
• 负责人: Karen L. Wooley
• 金额: $ 266.88万
• 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 2010-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623131
• 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)： 一个由科学家、纳米技术专家和医生组成的多学科团队将建立一个纳米技术卓越计划(PEN)，重点是与“用于诊断和治疗的集成纳米系统”相关的研究和教育活动。这支笔将包括来自华盛顿大学艺术与科学学院和医学院的研究人员，以及来自加州大学伯克利分校和圣巴巴拉分校的纳米技术专家。中心任务是开发一组具有良好特性和多功能的纳米制剂，这些制剂可以根据需要进行组装、标记、靶向、填充和激活，以结合诊断和治疗与NHLBI相关的各种疾病。总体实验策略将侧重于急性肺和全身血管损伤的生物模型(体外和体内)，以证明这些药物的有效性。这支笔有六个具体目标：(1)程序化、集成化纳米系统的制备和组装；(2)纳米结构在提高灵敏度的成像中的应用；(3)通过识别信使核糖核酸转录产物来成像基因表达；(4)纳米结构在治疗中的应用；(5)医学和材料科学家的跨学科教育和培训；以及(6)纳米技术发展的传播和翻译。将进行基础研究，以了解纳米技术应用于医学的潜在作用和限制，一些应用研究将致力于实施明确定义的纳米结构，用于诊断和治疗急性血管损伤和炎症，并在肺和心血管系统进行验证。将为新型多功能纳米结构的制备和表征开发一般方法，这些纳米结构可作为诊断和治疗药物的宿主，一旦它们完成其功能(目标1)，就可以安全地销毁。将分别通过正电子发射断层扫描、磁共振和光学成像对放射性、磁共振和光学标记的纳米结构进行增强成像能力的演示，通过细胞表面受体的配体将组织作为靶标(目标2)。还将开发细胞内靶向，以识别和“读取”信使核糖核酸，作为对在疾病状态下不受调控的基因产物或基因转移产物进行直接成像的一种手段(目标3)。预计这些新方法将作为一种新的分子成像形式普遍适用，它消除了对报告基因的需求。除了急性血管损伤的成像，还将开发使用一系列纳米材料提供各种治疗剂的治疗(目标4)。通过正规课程、讲习班和实验室轮换(目标5)，为学生和博士后的教育、培训和指导建立基础设施(目标5)，以及建立一个有效和基础广泛的传播结果、程序和方案的机制(目标6)，这将是国际笔会取得成功的关键。通过这些倡议，我们将为纳米科学和纳米技术的发展提供领导，这些纳米科学和技术可以影响整个21世纪的临床指导和能力。

项目成果

Identification and characterization of high affinity antisense PNAs for the human unr (upstream of N-ras) mRNA which is uniquely overexpressed in MCF-7 breast cancer cells.

• DOI: 10.1093/nar/gki968
• 发表时间: 2005
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Fang H;Yue X;Li X;Taylor JS
• 通讯作者: Taylor JS

FACILE PREPARATION OF NANOPARTICLES BY INTRAMOLECULAR CROSSLINKING OF ISOCYANATE FUNCTIONALIZED COPOLYMERS.

• DOI: 10.1021/ma900899v
• 发表时间: 2009-06-09
• 期刊: Macromolecules
• 影响因子: 5.5
• 作者: Beck JB;Killops KL;Kang T;Sivanandan K;Bayles A;Mackay ME;Wooley KL;Hawker CJ
• 通讯作者: Hawker CJ

Well-Defined Polymers Bearing Pendent Alkene Functionalities via Selective RAFT Polymerization.

• DOI: 10.1021/ma802057u
• 发表时间: 2008-12-09
• 期刊: MACROMOLECULES
• 影响因子: 5.5
• 作者: Ma, Jun;Cheng, Chong;Sun, Guorong;Wooley, Karen L.
• 通讯作者: Wooley, Karen L.

Rapid Synthesis of Block and Cyclic Copolymers via Click Chemistry in the Presence of Copper Nanoparticles.

• DOI: 10.1002/pola.24504
• 发表时间: 2011-02
• 期刊: JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
• 作者: Pressly, Eric D.;Amir, Roey J.;Hawker, Craig J.
• 通讯作者: Hawker, Craig J.

Supramolecular guests in solvent driven block copolymer assembly: From internally structured nanoparticles to micelles.

• DOI: 10.1039/c3py00750b
• 发表时间: 2013-10-07
• 期刊: Polymer chemistry
• 影响因子: 4.6
• 作者: Klinger D;Robb MJ;Spruell JM;Lynd NA;Hawker CJ;Connal LA
• 通讯作者: Connal LA