Collaborative Research: Unlocking the Potential of Active Lipid Vesicles for Directed Delivery and Controlled Release of Therapeutic Payloads

在目标位置定向输送和控制释放治疗有效载荷为开发下一代治疗输送系统提供了大量机会。脂质囊泡提供了一个多功能平台，以兼容和集成的方式完成这两个功能。这些脂泡是封闭的结构，有一层膜将囊泡内部与外部环境分开，类似于生物细胞膜。该奖项将利用脂囊的固有包裹能力来包裹治疗有效载荷和自推进颗粒，使囊泡能够定向运动到目标位置并受控释放包裹的有效载荷。这种基于囊泡的主动给药系统的成功开发将使未来的医疗保健受益。该奖项还将向K-12学生，特别是来自代表性不足群体的学生提供外展服务，以加强公众对该项目的挑战和潜在生物医学应用的了解。这项拟议的研究将新开发的自推进(或活性)粒子与新发现的对光诱导反应的囊泡反应融合在一起，创建了基于脂囊泡的综合治疗递送系统。通过将实验和理论研究相结合，该奖项旨在实现三个具体目标。第一个目标是研究由包裹的活性颗粒在内部驱动的脂泡的运动，实现脂泡的定向递送到目标位置。其次，将开发一种由光反应触发的非接触机制来诱导囊泡破裂，从而使其被包裹的内容物快速释放。最后，在上述目标中实现的功能将被组合在体外平台中，以展示通过使用活性囊泡在相关生物医学应用的目标位置定向递送和受控释放治疗药物。该项目的成功完成将促进对脂泡在这些非平衡过程中的复杂动力学的基本了解，确定关键的物理参数和设计原则，以指导基于活性囊泡的治疗递送系统的后续开发。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Directed delivery and controlled release of therapeutic payloads at targeted locations present substantial opportunities for developing the next generation of therapeutic delivery systems. Lipid vesicles offer a versatile platform to accomplish both functionalities in a compatible and integrated manner. These lipid vesicles are closed structures with a membrane that separates the interior of the vesicle from the outside environment, similar to the membrane of a biological cell. This award will leverage the innate encapsulation capacity of lipid vesicles to enclose both therapeutic payloads and self-propelled particles, enabling the vesicles to undergo directed motion to targeted locations and controlled release of the encapsulated payloads. Successful development of this active vesicle-based drug delivery system will benefit future healthcare. The award will also provide outreach to K-12 students, especially students from underrepresented groups, to enhance public understanding of the challenges and potential biomedical applications of the project. The proposed research fuses emerging developments of self-propelled (or active) particles with newly discovered vesicle responses to light-induced reactions to create an integrated therapeutic delivery system based on lipid vesicles. By combining experimental and theoretical investigations, this award aims to accomplish three specific objectives. The first objective is to examine the motion of lipid vesicles driven internally by encapsulated active particles, realizing the directed delivery of lipid vesicles to targeted locations. Secondly, a non-contact mechanism triggered by photoreactions will be developed to induce the rupture of a vesicle and thereby the rapid release of its encapsulated content. Finally, the functionalities achieved in the aforementioned objectives will be combined in an in-vitro platform to demonstrate directed delivery and controlled release of therapeutics at targeted locations for relevant biomedical applications via the use of active vesicles. Successful completion of this project will advance fundamental understanding of the complex dynamics of lipid vesicles in these non-equilibrium processes, identifying key physical parameters and design principles to guide subsequent developments of active vesicle-based therapeutic delivery systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.