Polymer Conformation, Dynamics, Morphology

我的研究重点是开发新的基础科学知识，聚合物作为材料的领域，其中一个可以对现代技术或医学产生影响。我们的大部分努力都致力于创造和研究在溶液中形成稳定胶体的聚合物物体，具有均匀的良好定义的形状和纳米或微米尺寸。该提案描述了两个广泛的项目，都在聚合物材料领域。一种是嵌段共聚物在溶液中的自组装。与I合作。Manners（布里斯托，英国），我们已经发表了开创性的论文，描述了前所未有的形成胶束在溶液中。这项工作在许多方面改变了科学家对嵌段共聚物胶束形成的看法，特别是当形成核的聚合物是结晶时。在这些研究中，聚二茂铁基硅烷（PFS）的核心形成块。它仍然是唯一类型的嵌段共聚物，可以形成具有均匀和可控长度的纳米线。在这里，我描述了新的实验，以了解机械为什么以及如何控制自组装是可能的，以及PFS聚合物分子如何折叠，因为它们添加到不断增长的胶束的末端，形成如此微小尺寸的晶体。由于这些纳米纤维的生长具有与人类疾病相关的淀粉样蛋白纤维形成共同的关键特征，但没有碎裂和聚集的并发症，PFS嵌段共聚物胶束生长的动力学研究可以提供有关影响溶液中淀粉样蛋白形成的因素的重要信息。 另一个项目是基于这样的想法，即我们可以应用我们在棒状胶体纳米结构方面的丰富经验来测试当前文献中的一个想法，即纳米棒状药物递送载体比球形纳米颗粒更有效地渗透到肿瘤中。我们建议在水中制备两种类型的棒状纳米胶体，一种基于纤维素纳米晶体，一种基于PFS纳米线胶束。我们将开发新的化学方法来合成这些纳米棒胶体，其中我们将控制棒的长度，横截面宽度和表面化学。然后，与C艾伦教授（药学）合作，我的学生将测试这些不同结构穿透多细胞肿瘤球体的能力，已知是体内实体肿瘤的良好模型，并将结果与更传统的球形纳米颗粒进行比较。虽然这些研究的重点完全是机械的，但结果将对这些材料在纳米医学中的应用产生重要影响。

My research is focused on developing new fundamental scientific knowledge about polymers as materials in areas where one can have an impact on modern technology or medicine. Much of our effort is devoted to the creation and study of polymer objects that form stable colloids in solution, with a uniform well-defined shape and with nanometer or micrometer dimensions. This proposal describes two broad projects, both in the area of polymer materials. One focuses on block copolymer self-assembly in solution. In collaboration with I. Manners (Bristol, UK) we have published seminal papers describing the unprecedented formation of nanofiber micelles in solution. This work has in many ways changed how scientists think about block copolymer micelle formation, particularly when the core-forming polymer is crystalline. In these studies, polyferrocenylsilane (PFS) was the core-forming block. It remains the only type of block copolymer that can form nanowires with a uniform and controllable length. Here I describe new experiments to understand mechanistically why and how such control of self assembly is possible, and how the PFS polymer molecules can fold as they add to the ends of the growing micelles to form crystals of such tiny dimensions. Because the growth of these nanofibers has key features in common with the formation of amyloid fibers associated with human diseases, but without the complications of fragmentation and aggregation, kinetic studies of PFS block copolymer micelle growth could provide important information about factors that affect nanofiber formation in solution. The other project is based on the idea that we can apply our extensive experience with rod-like colloidal nanostructures to test an idea in the current literature that nanosize rod-like drug delivery vehicles penetrate into tumors more effectively than spherical nanoparticles. We propose to prepare two types of rod-like nanocolloids in water, one based on cellulose nanocrystals and one based on PFS nanowire micelles. We will develop new chemistry to synthesize these nanorod colloids in which we will control the length of the rods, their cross section width, and their surface chemistry. Then, in collaboration with Prof C Allen (Pharmacy), my students will test the ability of these different structures to penetrate multicellular tumor spheroids, known to be good models for solid tumors in vivo, and compare the results with more traditional spherical nanoparticles. While the focus of these studies is entirely mechanistic, the results will have important implications for the application of these materials in nanomedicine.