Development of Chemical Platforms for Acoustically Controlled Molecular Delivery

项目摘要/摘要 Robb小组的研究重点是拓展聚合物新兴领域的前沿 机械力化学，利用机械力选择性地激活生产力 应力敏感分子中的化学变化称为机械团。我们的专业知识 是在分子设计和开发新的机械载体和反应策略方面， 能够获得刺激响应性聚合物，以应对各种领域的挑战 包括应力感应和机械触发的分子释放。我们的研究进展 从机械力化学反应的发展谈对机械力化学反应的基本认识 构效关系和新颖的分子设计原理，为 创造创新的材料。然而，关键的差距仍然存在，限制了翻译 聚合物机械力化学在生物和医学中的应用。在这份提案中，我们概述了 一种多方面的方法，用于开发能够实现声控的系统 生物相容聚焦法从机械力化学活性聚合物中的分子传递 超声波，特别是针对到目前为止仍遥不可及的生物应用。 在这笔米拉赠款的五年期间，我们将建立一个强大的机械载体平台 我们小组为机械触发的各种小分子有效载荷的释放而开发的 这利用了掩蔽的2-呋喃甲醇衍生物的机械力化学活化。而当 在实验室中，超声波通常用于聚合物的机械力化学活化， 在这样的声压下，溶解气体的强烈声空化具有很强的破坏性。 对组织来说，这使得它不适合大多数生物应用。补充我们的 开发新的化学物质，我们建议开发前所未有的系统来实现 利用聚焦超声远程控制生理状态下的机械力化学反应 具有空间和时间精度的条件。由新材料提供的独特协同效应 设计和生物兼容的声学激活策略将实现 聚合物机械力化学和建立作为未开发的触发释放的机械团 生物医学工具。我们的研究将以交付广泛的有效载荷为目标 从生物成像学到生物成像，展示了这种方法的力量，并为 在生物学、医学和人类健康方面的广泛应用。

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.