Polycation Beacons for Multiscale and Multimodal Imaging of Nucleic Acid Delivery

用于核酸输送多尺度和多模式成像的聚阳离子信标

• 批准号: 1105895
• 负责人: Theresa Reineke
• 金额: $ 42万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1105895&HistoricalAwards=false
• 关键词: Polycation; Beacons; Multiscale; Multimodal; Imaging

ID: MPS/DMR/BMAT(7623) 1105895 PI: Reinecke, Theresa ORG: University of MinnesotaTitle: Polycation Beacons for Multiscale and Multimodal Imaging of Nucleic Acid DeliveryINTELLECTUAL MERIT: The PI proposes to develop a novel family of twelve polycations that form nanoparticle complexes with nucleic acids that are nontoxic and effective at cellular entry, and to develop methods to track these nanoparticles via luminescence imaging (for intracellular trafficking on the nm/ìm scale) and magnetic resonance imaging (MRI, for bulk cell and tissue tracking/imaging on the ìm/mm scale). The specific objectives are: (1) To synthesize and characterize a novel family of twelve polymer structures that contain lanthanide chelates. The PI will systematically vary the following chemical properties of these polymer beacons: number of ethyleneamine groups, absence, presence, and size of the carbohydrates within the repeat unit, and polymer molecular weight. (2) To characterize water proton relaxivity, toxicity, and delivery efficiency for twelve polymer structures (chelated with Gd3+) and statistically compare the results to select three highly effective vehicles for delivery and imaging of pDNA and siRNA. (3) To examine the selected delivery beacons for pDNA and siRNA cellular trafficking via confocal microscopy (with the Eu3+ chelates) and MRI (with the Gd3+ chelates) in cultured cells to optimize the balance between imaging capability and delivery efficiency. (4) To establish an interactive mentoring and learning environment that successfully attracts undergraduate chemistry students to the McNair Scholars Program in an effort to unite teaching and scholarship with the excitement of performing interdisciplinary research and thus increase retention of disadvantaged students in the sciences.BROADER IMPACTS: This research is critical to advance many areas in need of delivery beacons, such as studies involving gene and epigenetic function, cellular signaling, therapeutic development, and regenerative medicine. The work will pave the way for higher information content imaging for therapeutic tracking in the lab and in the clinic, as well as aid development of specific medical therapies involving cellular-based genetic delivery. Students involved in this interdisciplinary program will gain uniquely broad and deep experience in fields ranging from synthetic chemistry and polymer science to molecular biology and imaging. Training students at this interface of different fields is essential to foster creative and innovative developments in research, increase the skills of our future workforce, and keep our country at the forefront of technological advancement. Involvement of the co-PI in the McNair Scholars Program targets current undergraduate students from disadvantaged backgrounds at Virginia Tech and prepares them to earn an advanced degree via formal graduate school preparation courses and mentoring. This program is designed to encourage and prepare financially disadvantaged and first generation college students and those from groups currently underrepresented to enter graduate education programs, primarily at the PhD level. The results from this project will be disseminated widely to the general public by the PIs, graduate and undergraduate and students involved in this work through publications, conference presentations, the web, to promote the research, mentoring, and educational programs are presented here.

ID：MPS/DMR/BMAT（7623）1105895 PI：Reinecke，Theresa ORG：明尼苏达大学标题：用于核酸输送的多尺度和多模式成像的聚阳离子Bestrom智能优势：PI建议开发一种新的十二种聚阳离子家族，这些聚阳离子与无毒且有效进入细胞的核酸形成纳米颗粒复合物，并开发通过发光成像跟踪这些纳米颗粒的方法。（用于nm/μ m尺度上的细胞内运输）和磁共振成像（MRI，用于μ m/mm尺度上的大量细胞和组织跟踪/成像）。 具体目标是：（1）合成和表征一个新的十二种含镧系元素螯合物的聚合物结构。 PI将系统地改变这些聚合物信标的以下化学性质：亚乙基胺基团的数量，重复单元内碳水化合物的存在、不存在和大小，以及聚合物分子量。 (2)表征十二种聚合物结构（与Gd 3+螯合）的水质子弛豫率、毒性和递送效率，并统计学比较结果，以选择三种高效载体用于pDNA和siRNA的递送和成像。 (3)通过共聚焦显微镜（使用Eu 3+螯合物）和MRI（使用Gd 3+螯合物）在培养细胞中检查pDNA和siRNA细胞运输的选定递送信标，以优化成像能力和递送效率之间的平衡。 (4)为了建立一个互动的指导和学习环境，成功地吸引本科化学学生麦克奈尔学者计划，努力结合教学和学术与执行跨学科研究的兴奋，从而提高在科学弱势学生的保留。这项研究对于推进许多需要传递信标的领域至关重要，例如涉及基因和表观遗传功能，细胞信号传导，治疗开发和再生医学的研究。 这项工作将为在实验室和临床中进行治疗跟踪的更高信息量成像铺平道路，并有助于开发涉及基于细胞的遗传传递的特定医学疗法。 参与这个跨学科计划的学生将获得从合成化学和聚合物科学到分子生物学和成像等领域的独特广泛而深入的经验。 在不同领域的这个界面上培养学生对于促进研究的创造性和创新性发展，提高我们未来劳动力的技能，并使我们的国家保持在技术进步的前沿至关重要。 共同PI参与麦克奈尔学者计划的目标是弗吉尼亚理工大学目前来自弱势背景的本科生，并为他们通过正式的研究生院准备课程和指导获得高级学位做好准备。 该计划旨在鼓励和准备经济上处于不利地位的第一代大学生和那些目前代表性不足的群体进入研究生教育课程，主要是在博士水平。 从这个项目的结果将被广泛传播给公众的PI，研究生和本科生和学生参与这项工作，通过出版物，会议演示，网络，以促进研究，指导和教育计划在这里介绍。