Diffusing Colloidal Probe Microscopy of Zwitterionic Nanoparticles

两性离子纳米粒子的扩散胶体探针显微镜

基本信息

批准号：
1947560
负责人：
Margarita Herrera-Alonso
金额：
$ 29.44万
依托单位：
Colorado State University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-28 至 2021-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1947560&HistoricalAwards=false
关键词：
Diffusing Colloidal Probe Microscopy Zwitterionic

项目摘要

Part I: Non-technical summaryRecent attempts to mimic the anti-biofouling properties of the external membrane of mammalian cells on synthetic substrates are increasingly relying on the use of zwitterionic-based materials, i.e., those bearing positively and negatively charged groups. In the context of biomaterials intended for drug delivery applications, surface modification methods that preclude aggregation, precipitation or clearance of diagnostic or therapeutic nanoparticles are particularly important to extend their circulation time in the body, and allow them to accumulate at specific sites through active targeting. Despite the tremendous potential of zwitterionic-based materials, little is known regarding weak interactions between particles and cells due to the limited sensitivity of existing techniques. In this work, the PIs will measure nanometer scale interactions between cells and zwitterionic-decorated particles using non-intrusive microscopy measurements of particle trajectories and analyses that reveal weak interactions. The PIs will use this method to evaluate interactions between nanoparticles functionalized with zwitterionic polymers with well-defined molecular architectures and cell surfaces. Outreach efforts will involve participation of undergraduate students in research, and community involvement through an education-based Latino outreach program and STEM Achievement in Baltimore Elementary Schools.Part II: Technical summaryThe proposed research will provide fundamental and technological insights into the molecular and processing parameters that produce zwitterionic (ZI) particles having the desired combination of specific and non-specific kT-scale interactions with various biomaterials. Non-specific repulsion between zwitterionic species and biomaterials will be understood, designed, optimized by controlling molecular architecture and structure, which will be quantitatively connected to direct sensitive measurements and models. Specific interactions to be investigated include sigma receptor-anisamide and CD44-hyaluronic acid interactions. The work proposed is divided into four tasks. The first deals with ZI polymer design, synthesis and characterization. The goal is to produce a library of materials with increasing architectural complexity that should translate into distinct surface properties. The second task is to examine ZI particle formation through either copolymer adsorption onto silica particles or self-assembly of highly branched amphiphilic macromolecules using processing conditions to affect ZI particle surface properties. The third task is to carry out diffusing probe measurements of ZI particles with model synthetic substrates, to ultimately establish the combination of polymer architecture and adsorption/self-assembly conditions that will result in desired non-specific repulsion. Having established this, the last task of this proposal is to use this knowledge to carry out diffusing probe measurements of specific interactions between ZI particles decorated with specific moieties and cancer cells. Such measurements will be performed for breast cancer cells to study interactions between hyaluronic acid and CD44 receptors, as well as, anisamide and sigma receptors. Each of the four tasks is part of an overarching plan to measure and interpret how particle-cell interactions are influenced by covalent attachment, orientation, and organization on synthetic and cell surfaces in nanobiotechnological applications.

第一部分：非技术摘要尝试模仿哺乳动物细胞对合成底物的外膜的抗生物形式特性越来越依赖于使用基于zwitterionic的材料的使用，即那些具有积极和负电荷的材料。在用于药物递送应用的生物材料的背景下，排除诊断或治疗纳米颗粒的聚集，降水或清除的表面修饰方法对于延长体内的循环时间并允许它们通过主动靶向在特定部位积聚。尽管基于zwitterionic的材料具有巨大的潜力，但由于现有技术的敏感性有限，颗粒与细胞之间的弱相互作用鲜为人知。在这项工作中，PI将使用粒子轨迹的非侵入性显微镜测量值测量细胞与Zwitterionic骨折颗粒之间的纳米尺度相互作用，并揭示了揭示弱相互作用的分析。 PI将使用此方法评估与具有明确定义的分子架构和细胞表面的Zwitterionic聚合物功能化的纳米颗粒之间的相互作用。推广工作将涉及本科生参与研究，并通过基于教育的拉丁裔宣传计划和巴尔的摩小学的STEM成就参与社区参与。第二部分：技术总结，拟议的研究将为分子和处理参数提供基本和技术的洞察力，这些研究将提供基本和技术的洞察力，该研究将产生特异性和非特异性KT尺度相互作用与各种生物材料的相互作用所需组合的zwittionic（Zi）颗粒。通过控制分子体系结构和结构，将了解，设计，优化Zwitterionic物种与生物材料之间的非特异性排斥，这将定量连接到直接敏感的测量和模型。要研究的特定相互作用包括西格玛受体 - 氨基酰胺和CD44-羟神ur酸相互作用。建议的工作分为四个任务。第一个涉及ZI聚合物设计，合成和表征。目的是生产具有增加建筑复杂性的材料库，应转化为不同的表面特性。第二个任务是使用加工条件使用共聚物颗粒上的共聚物吸附或高度分支的两亲性大分子的自组装来检查Zi颗粒的形成，以影响ZI粒子表面特性。第三个任务是用模型合成底物对Zi颗粒进行扩散的探针测量，以最终建立聚合物结构和吸附/自组装条件的组合，从而导致期望的非特异性排斥。确定了这一建议后，该提案的最后任务是利用这些知识来进行扩散的探针测量，对用特定部分和癌细胞装饰的Zi颗粒之间的特定相互作用进行了测量。将对乳腺癌细胞进行此类测量，以研究透明质酸和CD44受体之间的相互作用，以及Anisamide和Sigma受体。这四个任务中的每一个都是一个总体计划的一部分，旨在衡量和解释粒子相互作用如何受纳米元素技术应用中合成和细胞表面的共价依恋，方向和组织的影响。