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:
- 金额:$ 42.5万
- 依托单位:
- 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
- 来源:
- 关键词:AcousticsAddressAreaBiologicalBiologyChemicalsChemistryComplementCouplingDevelopmentFocused UltrasoundFoundationsGasesGrantHealthHumanLaboratoriesMasksMechanicsMedicineMolecularPhysiologicalPolymersProductivityReactionResearchStimulusStressStructure-Activity RelationshipSystemSystems DevelopmentTissuesTranslationsbioimagingbiomaterial compatibilitydesignfrontierfurfuryl alcoholinnovationmechanical forcenovelpressureprogramsremote controlsmall moleculesynergismtargeted deliverytheranosticstooltranslational applicationstranslational potential
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.
项目总结/摘要
Robb小组的研究重点是扩大聚合物新兴领域的前沿
机械化学,利用机械力选择性地激活生产力
压力敏感分子中的化学转化称为机械载体。我们的专业知识
是新机械载体和反应策略的分子设计和开发,
使人们能够获得刺激响应聚合物,以应对各种领域的挑战
包括应力传感和机械触发的分子释放。我们的研究进展
机械化学反应的基本理解,通过发展
构效关系和新的分子设计原则,为
创造创新材料。然而,关键的差距仍然存在,限制了翻译
聚合物机械化学在生物学和医学中的应用。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学控制的系统
使用生物相容性聚焦的机械化学活性聚合物的分子递送
超声波,特别是针对生物应用,迄今为止仍然遥不可及。
在MIRA赠款的五年期间,我们将建立一个强大的机械载体平台
在我们的小组中开发了用于机械触发释放各种小分子有效载荷的
其利用掩蔽的2-呋喃基甲醇衍生物的机械化学活化。而
超声波处理在实验室中常规用于聚合物的机械化学活化,
在这些声压下溶解气体的强声空化是高度破坏性的
使其不适合大多数生物应用。补充了我们
为了开发新的化学物质,我们建议开发前所未有的系统,
在生理条件下使用聚焦超声远程控制机械化学反应
具有空间和时间精度的条件。新型材料提供的独特协同作用
设计和生物相容性声学激活策略将实现
聚合物机械化学,并建立作为未开发的
生物医学工具我们的研究将针对广泛的有效载荷的交付,
从治疗诊断学到生物成像,展示了这种方法的力量,并为
在生物学、医学和人类健康中的多种应用。
项目成果
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