Enzyme-responsive Microgels

酶响应微凝胶

• 批准号: EP/I004998/1
• 负责人: Brian Saunders
• 金额: $ 13.15万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI004998%2F1
• 关键词: Enzyme; responsive; Microgels

Dynamic biological processes are tightly regulated by the catalytic activity of enzymes. The ability to direct, or otherwise interfere with, these processes holds promise for next generation medical interventions. It is in this context that we aim to develop new microgel particles that convert biocatalytic action of enzymes into mechanical responses. Our previous work has demonstrated that this is possible, in principle, and we now wish to explore this area further and address four challenges that will bring us a step closer to biomedical applications. They are: (i) establishing enzyme-responsive microgel particles that are two orders in magnitude smaller in size compared to our previously reported hydrogel beads and should have much faster response times; (ii) establishing enzyme-responsive microgel dispersions that display controlled mechanical response in the form of reversible fluid-to-gel transitions; (iii) establishing fully reversible systems that respond to combinations of enzymes (kinase/phosphatase); (iv) demonstrating, for the first time, the possibility of directing cellular responses using these enzyme-responsive microgel particles. Microgels are sub-micrometer sized polymer colloid particles that expand (swell) in a good solvent or when the particle charge increases. We will functionalise these microgel particles with peptide actuators that are recognised and cleaved by enzymes, thereby triggering a departure from the charge balance in the particles Uniquely, these enzyme-responsive microgels will operate locally, under aqueous conditions at constant pH and temperature which provides very significant advantages over existing stimuli-responsive materials in the context of biomedical applications. This collaborative project will provide two PhD students with exciting, multi-disciplinary projects in top class research environments. A successful outcome will open up new avenues of bioresponsive (nano) technologies for on demand drug delivery and minimally-invasive soft tissue repair.

动态生物过程受到酶催化活性的严格调控。指导或以其他方式干扰这些过程的能力为下一代医疗干预带来了希望。正是在这种背景下，我们的目标是开发新的微凝胶颗粒，将酶的生物催化作用转化为机械反应。我们以前的工作已经证明，这在原则上是可能的，我们现在希望进一步探索这一领域，并解决四个挑战，使我们更接近生物医学应用。它们是：（i）建立酶响应性微凝胶颗粒，其尺寸比我们先前报道的水凝胶珠小两个数量级，并且应该具有快得多的响应时间;（ii）建立酶响应性微凝胶分散体，其以可逆的流体-凝胶转变的形式显示受控的机械响应;（iii）建立响应于酶的组合的完全可逆的系统，（激酶/磷酸酶）;（iv）首次证明了使用这些酶响应性微凝胶颗粒指导细胞反应的可能性。微凝胶是亚微米尺寸的聚合物胶体颗粒，其在良溶剂中或当颗粒电荷增加时膨胀（溶胀）。我们将用被酶识别和切割的肽致动器功能化这些微凝胶颗粒，从而触发颗粒中电荷平衡的偏离。独特的是，这些酶响应微凝胶将在恒定pH和温度的水性条件下局部操作，这在生物医学应用的背景下提供了比现有刺激响应材料非常显著的优势。这个合作项目将为两位博士生提供一流研究环境中令人兴奋的多学科项目。一个成功的结果将开辟新的途径，生物反应（纳米）技术的按需药物输送和微创软组织修复。

项目成果

Using click chemistry to dial up the modulus of doubly crosslinked microgels through precise control of microgel building block functionalisation

使用点击化学通过精确控制微凝胶构建块功能化来提高双交联微凝胶的模量

• DOI: 10.1039/c4py01753f
• 发表时间: 2015
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: Farley R

Effects of crosslinker on the morphology and properties of microgels containing N-vinylformamide, glycidylmethacrylate and vinylamine.

交联剂对N-乙烯基甲酰胺、甲基丙烯酸缩水甘油酯和乙烯胺微凝胶形态和性能的影响

• DOI: 10.1016/j.jcis.2013.09.030
• 发表时间: 2014
• 期刊: Journal of colloid and interface science
• 影响因子: 9.9
• 作者: McCann J

One-Step Preparation of Uniform Cane-Ball Shaped Water-Swellable Microgels Containing Poly( N -vinyl formamide)

一步法制备均匀甘蔗球形水溶胀聚(N-乙烯基甲酰胺)微凝胶

• DOI: 10.1021/la204606v
• 发表时间: 2012
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Thaiboonrod S

Poly(vinylamine) microgels: pH-responsive particles with high primary amine contents

聚（乙烯胺）微凝胶：具有高伯胺含量的 pH 响应性颗粒

• DOI: 10.1039/c3sm27728c
• 发表时间: 2013
• 期刊: Soft Matter
• 影响因子: 3.4
• 作者: Thaiboonrod S