Development of Chemical Platforms for Acoustically Controlled Molecular Delivery

声控分子传递化学平台的开发

基本信息

批准号：
10714467
负责人：
Maxwell J Robb
金额：
$ 42.5万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-04-30
项目状态：
未结题

项目摘要

Project Summary / Abstract Research in the Robb group is focused on expanding the frontiers of the emergent field of polymer mechanochemistry, where mechanical force is harnessed to selectively activate productive chemical transformations in stress-sensitive molecules known as mechanophores. Our expertise is in the molecular design and development of new mechanophores and reaction strategies, enabling access to stimuli-responsive polymers that address challenges in a variety of areas including stress sensing and mechanically triggered molecular release. Our research advances the fundamental understanding of mechanochemical reactivity through the development of structure–activity relationships and novel molecular design principles, providing a foundation for creating innovative materials. Nevertheless, critical gaps remain that have limited the translation of polymer mechanochemistry to applications in biology and medicine. In this proposal, we outline a multifaceted approach for the development of systems that enable acoustically controlled molecular delivery from mechanochemically active polymers using biocompatible focused ultrasound, specifically targeting biological applications that have thus far remained out of reach. In the five-year period of this MIRA grant, we will build on a powerful mechanophore platform developed in our group for the mechanically triggered release of diverse small molecule payloads that leverages the mechanochemical activation of masked 2-furylcarbinol derivatives. While ultrasonication is routinely used in the laboratory for the mechanochemical activation of polymers, the strong acoustic cavitation of dissolved gases at these acoustic pressures is highly destructive to tissues, making it incompatible for most biological applications. Complementing our development of novel chemistries, we propose to develop unprecedented systems for achieving remote control of mechanochemical reactions using focused ultrasound under physiological conditions with spatial and temporal precision. The unique synergy provided by novel materials design and biocompatible acoustic activation strategies will realize the translational potential of polymer mechanochemistry and establish mechanophores for triggered release as an untapped biomedical tool. Our research will target the delivery of a wide range of payloads useful for theranostics to bioimaging that demonstrate the power of this approach and pave the way toward diverse applications in biology, medicine, and human health.

项目摘要 /摘要 ROBB组的研究重点是扩大聚合物新兴领域的边界机械化学，利用机械力来选择性激活产品应力敏感分子中的化学转化称为机械团。我们的专业知识是在新机械载体和反应策略的分子设计和开发中，使能够访问刺激反应性聚合物，以应对各个领域的挑战包括应力敏感性和机械触发的分子释放。我们的研究进展通过发展对机械化学反应性的基本理解结构 - 活动关系和新颖的分子设计原理，为创新材料。然而，仍然存在限制翻译的关键差距聚合物机械化学在生物学和医学中的应用中。在此提案中，我们概述了用于开发系统的多方面方法，可以准确控制使用焦点聚焦从机械活性聚合物中分子递送超声波，特异性针对迄今为止尚无法触及的生物学应用。在此Mira赠款的五年中，我们将在强大的机械电池平台上建立在我们的小组中开发，用于机械触发潜水员小分子有效载荷的释放这利用了掩盖的2-富甲醇衍生物的机械化学激活。尽管超声化通常用于实验室，用于聚合物的机械化学激活，在这些声音压力下溶解的气体的强声气水是高度破坏性的到组织，使其在大多数生物学应用中不兼容。补充我们开发新型化学，我们建议开发前所未有的系统来实现在生理下使用聚焦超声对机械化学反应的遥控器具有空间和临时精度的条件。新型材料提供的独特协同作用设计和生物相容性的声学激活策略将实现转化潜力聚合物机械化学并建立用于触发释放的机械算术，作为未开发的生物医学工具。我们的研究将针对提供广泛有效载荷的针对疗法的生物成像，证明了这种方法的力量，并铺平了道路生物学，医学和人类健康中的多种应用。