CAREER: Implementing a Stealth-to-Targeting Switch in Model Colloidal Carriers

职业生涯：在胶体载体模型中实现隐身到瞄准的转换

• 批准号: 0847436
• 负责人: Valeria Milam
• 金额: $ 50万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0847436&HistoricalAwards=false
• 关键词: CAREER; Implementing; Stealth; Targeting; Switch

ID: MPS/DMR/BMAT(7623) 0847436 PI: Milam, Valeria ORG: Georgia TechTitle: CAREER: Implementing a Stealth-to-Targeting Switch in Model Colloidal CarriersThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: This proposal is concerned with implementing a dynamic stealth-to-targeting switch in model colloidal carriers. Specific motivation for this work lies in the therapeutic limitations of current drug delivery vehicles possessing either stealth or targeting capabilities. By incorporating a dynamic stealth-to-targeting switch, the proposed research has the potential to pave the way for a new generation of drug carrier systems that fully realize their therapeutic index through dramatic improvements in both circulation time and desired targeting abilities for injured, malignant, or diseased tissue. To implement a finely controlled transition between stealth and targeting states, the proposed approach employs DNA as dynamic macromolecular linkers initially to mask, and then to reveal targeting ligands on model colloidal carriers. The central aim is to tailor the timing of DNA-mediated targeting events through directed hybridization events of DNA strands immobilized on the carrier surface. The challenge lies in controlling the stability and interactions of DNA in order to tailor the kinetics and extent of carrier ?activation.? To address this challenge, the proposed work will explore sequence characteristics, such as affinity differences between various oligonucleotide strands, to induce particular structural changes in the DNA strands and thereby modulate ligand presentation in a model carrier system. BROADER IMPACTS: The integrated education plan involves initiatives geared towards both high school students and engineering college students. The motivation for this plan lies in the need to (1) increase young students? exposure and interest in engineering, particularly to materials science and engineering (MSE) and (2) train engineering students to address the synergistic roles of materials and biological systems in bio-related materials applications. The first part of the educational plan involves developing and implementing a Materials Science and Technology (MST) course in a local high school. The objective of this laboratory-intensive course is to physically and intellectually engage young students in reinforcing and applying fundamental scientific and engineering principles using materials as a practical learning tool. A series of experiments on various classes of materials, including biomaterials, will be incorporated into the course topics. The target audiences for this hands-on, minds-on educational approach are (a) underrepresented groups in engineering for whom pre-university educational initiatives would help attract them to pursue degrees and careers in engineering and (b) the at-risk population of high school students who often possess the capability, but lack the motivation to take upper level, college preparatory courses in science and math. The teaching modules will be made freely available for public distribution through the MSE website at GA Tech. The second part of the educational plan involves developing MSE courses to address the structure and properties of both the biological and materials systems at biological-material interfaces. The objective is to extend a central paradigm in MSE ? structure-property relationships ? to include biological systems, consistent with ongoing efforts in our MSE program aimed at integrating biorelated topics in the curriculum.

ID: MPS/DMR/BMAT(7623) 0847436 PI: Milam， Valeria ORG: Georgia TechTitle：职业：在胶体载体模型中实现隐身到目标转换该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。智力优势：该建议涉及在模型胶体载体中实现动态隐身到目标切换。这项工作的具体动机在于当前药物递送载体具有隐身或靶向能力的治疗局限性。通过结合动态的隐身到靶向转换，该研究有可能为新一代药物载体系统铺平道路，通过显着改善循环时间和对受伤、恶性或病变组织的期望靶向能力，充分实现其治疗指标。为了实现在隐身状态和靶向状态之间的精细控制过渡，该方法首先使用DNA作为动态大分子连接体来掩盖，然后在模型胶体载体上显示靶向配体。中心目标是通过固定在载体表面的DNA链的定向杂交事件来调整DNA介导的靶向事件的时间。挑战在于控制DNA的稳定性和相互作用，以调整载体激活的动力学和程度。为了应对这一挑战，本研究将探索序列特征，如不同寡核苷酸链之间的亲和力差异，以诱导DNA链中的特定结构变化，从而调节模型载体系统中的配体呈现。更广泛的影响：综合教育计划包括面向高中学生和工程学院学生的举措。这个计划的动机在于需要(1)增加年轻学生？对工程，特别是材料科学与工程（MSE）的接触和兴趣，以及(2)培养工程专业的学生解决材料和生物系统在生物相关材料应用中的协同作用。教育计划的第一部分涉及在当地一所高中开发和实施材料科学与技术（MST）课程。这门实验密集型课程的目标是让年轻学生在物理和智力上加强和应用基础科学和工程原理，并将材料作为实用的学习工具。一系列不同种类材料的实验，包括生物材料，将被纳入课程主题。这种动手、专注的教育方法的目标受众是(a)工程领域代表性不足的群体，对他们来说，大学预科教育计划将有助于吸引他们攻读工程学位和职业生涯；(b)处于风险中的高中生群体，他们通常有能力，但缺乏动力参加更高水平的大学科学和数学预科课程。教学模块将通过GA Tech的MSE网站免费向公众发布。教育计划的第二部分涉及开发MSE课程，以解决生物和材料系统在生物-材料界面上的结构和特性。目标是扩展MSE的中心范式。结构-属性关系？包括生物系统，这与我们的MSE项目旨在将生物相关主题纳入课程的持续努力是一致的。