POWRE: Polysomes: Biologically-Inspired Vesicles of Block Copolymers for Targeted Delivery and Controlled Release Applications

Cts-9973524 Santore，Maria MLeHigh University磷脂双层囊泡或脂质体是几十年来研究的重点，它构成了细胞膜的基础，并一直处于生物技术和非生物应用的囊泡技术的核心。人们普遍认为，像磷脂这样的表面活性物质提供了很大的化学变化可能性，应该是囊泡壁的主要构建块。然而，拟议的客座教授职位和后续研究计划的动机是最近的一项发现，即某些共聚物，即使是以聚乙烯(PE)和聚氧乙烷(PEO)等商品材料为基础的共聚物，也会形成看起来类似于经典脂质体的囊泡或“多聚体”。多聚体有可能使靶向递送、微反应器和微生物发酵器、传感器和致动器等技术发生革命性变化，甚至形成人造细胞的基础，因为它们可以拓宽双层膜存活的条件范围，并增加可以工程制作成膜的性质类型。这项建议解决了多聚体技术开发和实施必须解决的一些基本问题。第一个探索是建立形成多聚体的共聚物化学和结构的范围，以及这些膜对pH和化学中的扰动的稳定性。在写这份提案的时候，只有一个系统被检查并被证明形成囊泡。这项工作为预测其他也可能成功的化学提供了一种策略。下一个问题是可以达到什么范围的基本膜性能(机械性能和横向扩散率)，以及这些与磷脂微囊的比较如何。由于多聚体的最终性能将取决于它们的通透性和官能化部分可以被结合到膜中的程度，因此这些问题也将被考虑到多聚体。最后，在许多模拟细胞行为的受控递送应用和实例中，多聚体与其他多聚体和外表面的粘附性将是至关重要的。拟议的计划包括这一领域的试点研究，以形成休假以外的工作基础。战俘要求提供资金，以支持桑托尔教授在宾夕法尼亚大学哈默教授的实验室度过一年的休假，多倍体是在那里首次被发现的。该实验室是基础囊泡黏附研究的理想实验室。在休假期间，桑托雷将学习制造和操作囊泡的基本技术，这些知识是利哈伊学不到的。将致力于解决哪些共聚物形成多聚体以及多聚体膜的机械、扩散和渗透性能的问题。此外，在访问教授期间，将开始研究囊泡黏附和将特殊分子结合到多聚体壁上的问题。最后两个副题的结果将构成利哈伊未来项目的基础，超越客座教授的职位，以及Hammer和Santore之间未来的合作。请拨经费，用于支付桑托雷教授休假期间的工资，以及利哈伊大学在休假期间用于囊泡研究的基本设备。关键词：材料；膜；囊泡；POWRE；生物医学；表面活性剂

CTS-9973524Santore, Maria MLehigh UniversityPhospholipid bilayer vesicles, or liposomes, a focus of research for several decades, form the basis for cellular membranes and have been at the core of vesicle technology for biotechnological and non-bio applications alike. It has generally been assumed that surfactants like phospholipids, which offer large possibilities for chemical variations, should be the primary building blocks for vesicle walls. The proposed Visiting Professorship and follow-up research program was, however, motivated by the extremely recent discovery that certain copolymers, even those based on commodity materials such as polyethylene (PE) and polyethylene oxide (PEO), form vesicles or "polysomes" that appear similar to classical liposomes. Polysomes have the potential to revolutionalize technologies such as targeted delivery, microreactors and microfermentors, sensors and actuators, and even form the basis of artificial cells because they can broaden the range of conditions where bilayer membranes can survive and they increase the types of properties that can be engineered into membranes.This proposal addresses a number of fundamental issues which must be resolved in order for polysome technology to be developed and implemented. The first quest is to establish the range of copolymer chemistries and architectures that form polysomes, and the robustness of these membranes to pH and perturbations in the chemistry. At the time this proposal was written, only one system was examined and shown to form vesicles. This work presents a strategy for anticipating other chemistries which may also succeed. The next issue is what range of basic membrane properties can be achieved (mechanical properties and lateral diffusivity) and how these compare with phospholipid vesicles. Since the ultimate performance of polysomes will depend on their permeability and the extent to which functionalized moieties can be incorporated into the membrane, the issues will also be considered with polysomes. Finally, in many controlled delivery applications and instances that mimic cell behavior, the adhesion of the polysome with other polysomes and external surfaces will be critical. The proposed program includes pilot studies in this area to form the basis of work beyond the sabbatical leave.POWRE monies are requested to support a sabbatical leave for Professor Santore to spend a year in Professor Hammer's lab at the University of Pennsylvania, where polysomes were first discovered. This laboratory is well-quipped for the fabrication and study of basic vesicle adhesion studies. During the sabbatical, Santore will learn the basic techniques for fabricating and manipulating vesicles, knowledge that could not be acquired at Lehigh. Work will be done towards the questions of which copolymers form polysomes and the mechanical, diffusional, and permeation properties of polysomes membranes. Also during the Visiting Professorship, work will be initiated to study the issues of vesicle adhesion and the incorporation of specialized molecules into the polysome wall. Results from these last tow subtopics will form the foundation for future programs at Lehigh, beyond the Visiting Professorship, and future collaborations between Hammer and Santore. Funds are requested for of Professor Santore's salary during the sabbatical, and basic equipment for vesicle studies at Lehigh beyond the sabbatical leave.Key Words: Materials; Membranes; Vesicle; POWRE; Biomedical; Surfactants