CAREER: Responsive Biomimetic Strategies in Drug Delivery: Molecular Brush Oligomers

职业：药物输送中的响应仿生策略：分子刷低聚物

• 批准号: 1151535
• 负责人: Margarita Herrera-Alonso
• 金额: $ 51.38万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1151535&HistoricalAwards=false
• 关键词: CAREER; Responsive; Biomimetic; Strategies; Drug

TECHNICAL ABSTRACT:This research explores the use of amphiphilic brush copolymers to build environmentally responsive filamentous nanostructures for targeted drug delivery applications. The objective of this proposal is to synthesize constructs that enhance delivery by controlling carrier-cell interactions through shape-dependent environmentally tunable mechanisms. The PI will design oligomers of molecular brushes containing environmentally responsive moieties along the backbone and between adjacent brushes to produce carriers of hydrophobic solutes with controllable spatial and/or temporal 3-D structure, surface chemistry, and mechanical properties. The biomimetic aspect of these constructs relies on the fact that they are designed after the segmental nature of secreted mucins. The programmable aspect targets their environmentally triggered de-oligomerization and conformational transitions. To address this scientific challenge the PI will utilize well-defined polymer synthesis and conjugation methods and engineer surface functionalization techniques. The specific objectives of this proposal are: (1) to design, synthesize, and characterize amphiphilic core-shell molecular brushes with pH-sensitivity and then carry out their oligomerization; (2) to study the hydrophobic collapse of molecular brush oligomers, solute loading, and the triggered shape change and de-oligomerization of brush filaments; and (3) to synthesize surface patterned particles from molecular brushes by the copolymerization of pre-assembled building blocks.NON-TECHNICAL ABSTRACT:The proposed research will provide valuable information regarding the design of new polymers inspired by nature. The knowledge gained through the completion of this project will provide us with a better understanding of the structure/property relationships of these building blocks and will allow us to use them in the context of other bioinspired materials applications. If successful, this project will advance drug-carrier design by harnessing the chemical flexibility and unique physical properties of stimuli-responsive polymeric biomaterials to control carrier-cell interactions across the micro-to-nano length scale. The broader impact of the proposed CAREER program will combine the PI's research interest in the development of 'intelligent' polymer-based biomaterials with an educational program targeted to generate interest in the field throughout the pre-undergraduate educational levels, particularly among under-represented student populations. By creating an engaging and inspiring research environment, the PI will seek to continually interest undergraduate and graduate students in the field of stimuli-responsive polymer systems and drug delivery. The nature of the proposed research should provide students with stimulating challenges across disciplines, a comprehensive education in polymer science from theoretical and experimental perspectives, and with the tools to address a problem with creativeness and a critical mindset.

技术摘要：这项研究探讨了两亲性刷子共聚物的使用来建立针对有针对性药物递送应用的环境响应式丝状纳米结构。该提案的目的是合成通过控制形状依赖性环境调谐机制来控制载体细胞相互作用来增强输送的构建体。 PI将设计沿骨架和相邻刷子之间的分子刷的低聚物，以产生具有可控的空间和/或时间3-D结构，表面化学和机械性能的疏水质溶质载体。这些结构的仿生方面依赖于以下事实：它们是根据分泌粘蛋白的分段性质设计的。 可编程的方面针对其环境触发的去寡聚化和构象转变。为了应对这一科学挑战，PI将利用定义明确的聚合物合成和共轭方法以及工程师表面功能化技术。该提案的特定目标是：（1）用pH敏感性设计，合成和表征两亲芯壳分子刷，然后进行寡聚； （2）研究分子刷子寡聚物的疏水崩溃，溶质负载以及触发的形状变化和刷丝丝的脱落； （3）通过预组装构建块的共聚来从分子刷中合成表面图案颗粒。Non-technical摘要：拟议的研究将提供有关受自然启发的新聚合物设计的有价值的信息。 通过完成该项目获得的知识将使我们更好地了解这些构建基块的结构/财产关系，并使我们能够在其他生物启发的材料应用程序中使用它们。 如果成功，该项目将通过利用刺激性反应性聚合物生物材料的化学柔韧性和独特的物理特性来促进药物载体设计，以控制整个微型到纳米长度范围内的载载细胞相互作用。 拟议职业计划的更广泛影响将结合PI对基于“智能”聚合物的生物材料的发展的研究兴趣与一个旨在在整个较低的教育水平上引起该领域的兴趣的教育计划，尤其是在代表性不足的学生中人群。通过创建引人入胜且鼓舞人心的研究环境，PI将寻求在刺激反应性聚合物系统和药物输送领域的本科生和研究生不断感兴趣。拟议的研究的性质应为学生提供跨学科的挑战，从理论和实验角度从聚合物科学领域进行全面的教育，并使用工具来解决创造力和批判性心态的问题。