Spatially Patterned Nano/Microparticles to Traverse Biological Barriers

空间图案纳米/微粒跨越生物屏障

• 批准号: 1507238
• 负责人: Todd Sulchek
• 金额: $ 38.5万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1507238&HistoricalAwards=false
• 关键词: Spatially; Patterned; Nano; Microparticles; Traverse

Non-Technical: This award by the Biomaterials program in the Division of Materials Research is to create and study novel multifunctional particles which mimic bacterial processes for beneficial purposes such as drug delivery. The biomaterial is based upon a newly created form of Janus particle, which displays biological ligands on a particle in a spatially distinct manner, for example with a right and left hemisphere. Since the particle ligands are clustered and polarized, highly effective biological reactions can be harnessed by the particle to enter cells and translocate within cells. Interactions of the particles with a model of the blood brain barrier will be studied to understand the efficiency of particle delivery to the brain. This project will provide interdisciplinary training opportunities to graduate and undergraduate students on biomaterials, microtechnology, and neuroscience. The research activities will also promote the recruitment and mentoring of diverse students in cutting-edge scientific techniques through outreach in the Atlanta public high schools.Technical: Particles that can actively traverse biological barriers, such as the blood-brain barrier, would be highly beneficial for a variety of basic science and applied purposes. Traversing biological barriers is routinely demonstrated by some pathogens. For example, the bacterium Listeria monocytogenes can asymmetrically express specific proteins to efficiently internalize into cells, escape a phagosome, and actuate within the cell cytosol via nucleated actin polymerization to escape the cell. However, designing biomaterials that can accomplish these tasks is a challenge. This study aims to create new, multifunctional particles which mimic pathogenic mechanisms to enter an epithelial cell layer and actively transport within the cell to exit on the basal side. Janus particles will be designed as a new class of multifunctional, topographically distinct particles that can autonomously transverse an epithelial barrier. These particles will be created with micropatterning technologies to produce chemically-distinct regions on the particle surface to which effector proteins are linked to mediate each step of transcytosis. The investigators hypothesize that high density of effector ligands through topographic separation will engineer particles with potent and coordinated ligand-mediated processes characteristically achieved by biological organisms. Interactions of the particles with a model of the blood brain barrier will be studied to understand the efficiency of particle delivery to and within the brain. The proposed program will help inspire graduate and undergraduate students from diverse disciplines and backgrounds to study how microfabrication technologies can harness bio-inspired effectors to create new biomimetic materials to widely impact the biosciences. Additionally the program will develop new curriculum for engineers and scientists to design multifunctional particles, which will further include the recruiting of high school students and teachers to contribute to research studies.

非技术：该奖项由材料研究部的生物材料项目授予，旨在创造和研究新型多功能颗粒，这些颗粒模拟细菌过程，用于药物输送等有益目的。该生物材料基于新创建的Janus粒子形式，其以空间上不同的方式在粒子上显示生物配体，例如具有右半球和左半球。由于粒子配体是聚集和极化的，因此粒子可以利用高效的生物反应进入细胞并在细胞内移位。将研究颗粒与血脑屏障模型的相互作用，以了解颗粒递送到大脑的效率。该项目将为研究生和本科生提供生物材料、微技术和神经科学方面的跨学科培训机会。研究活动还将通过在亚特兰大公立高中的推广活动，促进招募和指导不同学生掌握尖端科学技术。技术：能够主动穿越生物屏障（如血脑屏障）的粒子将对各种基础科学和应用目的非常有益。一些病原体通常会穿越生物屏障。例如，细菌单核细胞增多性李斯特菌可以不对称地表达特异性蛋白质以有效地内化到细胞中，逃离吞噬体，并且在细胞胞质溶胶内通过有核肌动蛋白聚合致动以逃离细胞。然而，设计能够完成这些任务的生物材料是一个挑战。这项研究旨在创造新的多功能颗粒，模拟致病机制进入上皮细胞层，并在细胞内积极运输，在基底侧离开。Janus颗粒将被设计为一类新的多功能的，地形不同的颗粒，可以自主穿越上皮屏障。这些颗粒将用微图案化技术产生，以在颗粒表面上产生化学上不同的区域，效应蛋白连接到该区域以介导转胞吞的每个步骤。研究人员假设，高密度的效应配体通过地形分离将工程粒子与强大的和协调的配体介导的过程，生物有机体的特点实现。将研究颗粒与血脑屏障模型的相互作用，以了解颗粒递送到大脑和大脑内的效率。拟议的计划将有助于激励来自不同学科和背景的研究生和本科生研究微制造技术如何利用生物启发效应器来创造新的仿生材料，以广泛影响生物科学。此外，该计划还将为工程师和科学家开发新的课程，以设计多功能粒子，其中还将包括招募高中学生和教师为研究做出贡献。