Monodisperse, Thermoresponsive Microgels Based on Poly(ethylene Glycol) Derivative Polymers

技术综述：合成单分散聚合物胶体通常是研究自组装过程的第一步，对于纳米结构材料的制备尤为重要。目前可用的聚合物胶体包括聚苯乙烯、聚甲基丙烯酸甲酯(PMMA)和聚N-异丙基丙烯酰胺(PNIPAM)微球及其衍生物。这个拟议项目的目标是在聚乙二醇衍生物聚合物的基础上，加入这些著名的聚苯乙烯、PMMA和PNIPAM胶体，创建新的单分散、温度敏感型聚合物胶体。其核心思想是通过沉淀聚合法将聚乙二醇乙醚甲基丙烯酸酯(PEGETH2 MA)、聚乙二醇甲基醚甲基丙烯酸酯(PEGMEA)、聚乙二醇丙烯酸酯(PEGA)及其衍生物共聚合成这些胶体。前两个组分提供接近生理温度的低临界溶液温度(LCST)，而第三个组分(PEGA)提供官能团。在适当的化学组成和反应条件下，可以得到粒径分布非常窄的聚乙二醇衍生物微凝胶。因此，这些聚乙二醇衍生物微凝胶可以作为构建块来制备具有胶体晶体结构的水凝胶。这一拟议项目包括五个具体目标。第一种方法是合成和表征单分散性、温敏性和具有官能团的聚乙二醇衍生物微凝胶。第二个目标是首先合成可生物降解的聚乙二醇聚乳酸大分子单体，然后将其用作微凝胶的交联剂，从而合成可生物降解的聚乙二醇衍生物微凝胶。通过建立结晶动力学与微凝胶的柔软性(低机械模数)之间的关系，将探索聚乙二醇衍生物微凝胶的自组装过程。(目标3)利用聚乙二醇衍生物微凝胶作为交联剂和光衍射晶格，合成具有胶体晶体结构的水凝胶(目标4)。目的五是制备聚乙二醇微胶体胶体，并建立描述胶体胶体等凝胶壳的溶胀动力学的理论模型。非技术总结：这一项目具有创新性，因为如果成功，它将导致一类具有热响应特性和单分散尺寸分布的新型聚合物胶体。与疏水性的聚苯乙烯微球和PMMA微球不同，所提出的聚乙二醇衍生物粒子是亲水性的，并且在生理温度附近具有热响应性体积相变。与弹性模数极软的PNIPAM微凝胶不同，可行性研究表明，聚乙二醇衍生物微凝胶将更致密、更硬、更容易形成结晶结构。此外，在过去的二十年里，对热响应性聚合物微凝胶的研究主要集中在PNIPAM及其衍生物上。然而，PNIPAM的特殊热敏特性还没有转化为生物医学上的突破。其中一个主要障碍是PNIPAM单体是否致癌或致畸。因此，寻找一种可替代PNIPAM的生物相容性聚合物微凝胶将是该领域的主要进展之一。拟议的项目将为两名研究生提供直接支助，并扩大代表性不足群体的参与。该计划将把其本科生教育努力与三个现有的促进研究经验的计划相结合：德克萨斯数学与科学学院、北卡罗来纳大学罗纳德·F·麦克奈尔学士学位后成就计划和NSF-UNT REU暑期计划。从这个建议的跨学科项目中，研究生和本科生都将在聚合物、胶体和纳米结构材料快速增长的领域获得宝贵的实验和分析技能。这项研究中建立的基础科学不仅将对聚合物科学产生影响，而且将对生物医学技术产生影响。

TECHNICAL SUMMARY:Synthesizing monodisperse polymer colloids is usually the first step toward the study of self-assembling processes and especially important for the fabrication of nanostructured materials. The current available polymer colloids include polystyrene, polymethyl methacrylate (PMMA) and poly-N-isopropylacrylamide (PNIPAM) spheres and their derivatives. The objective of this proposed project is to create new monodisperse, thermo-responsive polymer colloids based on poly(ethylene glycol) derivative polymers, joining in these well-known colloids of polystyrene, PMMA, and PNIPAM. The central idea is to synthesize these colloids with copolymerization of poly(ethylene glycol) ethyl ether methacrylate (PEGETH2MA), poly(ethylene glycol) methyl ether methacrylate (PEGMEA), poly(ethylene glycol) acrylate (PEGA) and their derivatives using precipitation polymerization method. The first two components give the low critical solution temperature (LCST) near the physiological temperature while the third component (PEGA) provides a functional group. Under proper chemical compositions and reaction conditions, PEG derivative microgels with a very narrow size distribution may be obtained. As a result, these PEG derivative microgels can be used as building blocks to fabricate hydrogels with colloidal crystal structures. This proposed project consists of five specific aims. The first is to synthesize and characterize PEG derivative microgels that should be monodisperse, thermoresponsive, and with functional groups. The second aim is to synthesize biodegradable PEG derivative microgels by first synthesizing biodegradable PEG-polylactic acid macromer and then using them as crosslinkers for microgels. Self-assembling processes of the PEG derivative microgels will be explored by establishing the relationship between crystallization kinetics with the softness (low mechanical modulus) of the microgels. (Aim 3) Hydrogels with colloidal crystalline structures will be synthesized using PEG derivative microgels as both crosslinkers and as a light diffraction lattice (Aim 4). Aim five will focus on preparation of PEG-microgels-based colloidosomes and build a theoretical model that will describe swelling kinetics of a gel shell such as colloidosomes.NON-TECHNICAL SUMMARY:This proposed project is innovative because if successful, it will lead to a new class of polymer colloids that have thermal responsive properties and monodisperse size distribution. In contrast to polystyrene spheres and PMMA spheres that are hydrophobic, the proposed PEG derivative particles are hydrophilic and have a thermally responsive volume phase transition near the physiological temperature. Different from PNIPAM microgels that are extremely soft in terms of elastic modulus, the PEG derivative microgels will be denser, harder and easier to form a crystalline structure as revealed by the feasibility study. Furthermore, in the past two decades the most research on thermally responsive polymer microgels has focused on PNIPAM and its derivatives. However, the extraordinary thermo-sensitive properties of PNIPAM have not been transferred into a biomedical breakthrough. One of the major hurdles is that PNIPAM monomer is carcinogenic or teratogenic. Thus, finding a biocompatible polymer microgel replacement of PNIPAM will be one of the major advancements in this field. The proposed project will provide direct support for two graduate students and broaden the participation of underrepresented groups. This program will integrate its undergraduate educational efforts with three existing programs that promote research experiences: the Texas Academy of Mathematics and Science, the Ronald F. McNair Post-baccalaureate Achievement Program at UNT, and NSF-UNT REU summer program. From this proposed inter-disciplinary project, both graduate and undergraduate students will gain valuable experimental and analytical skills in the rapidly growing fields of polymers, colloids and nanostructured materials. The basic sciences established in this research will have impacts not only in polymer sciences but also in biomedical technology.