Responsive Hybrid Oleosin Nanomaterials

响应性杂化油质蛋白纳米材料

• 批准号: 1609784
• 负责人: Daniel Hammer
• 金额: $ 39万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1609784&HistoricalAwards=false
• 关键词: Responsive; Hybrid; Oleosin; Nanomaterials

Non-technical A goal of materials research is to make responsive, biocompatible materials that can respond uniquely to environmental conditions and also be targeted to specific sites in the body. The development of carriers that can specifically target sites of disease would increase the efficacy of treatments and reduce toxic side effects of drugs delivered systemically. Nano-materials, such as spherical micelles and vesicles, can be used to carry large payloads of drugs and imaging agents. For all of the promise of targeted drug delivery, there are relatively nanomaterials that afford robust, targeted delivery while being responsive to environmental conditions. To meet this significant need, the PI's goal is to make a class of nanocarriers, made from a naturally occurring plant protein called oleosin, that can target specific sites, be turned on for drug delivery only in specific locations, and have reduced immunogenicity. The PI will introduce responsive domains into the protein using recombinant biotechnology, and demonstrate how carriers made of the protein can bind to sites of inflammation using a flow chamber lined with endothelial cells, the cells which line blood vessels.This work will also impact the lives of students who are trained in the PI's laboratory. The graduate students who work on this project will be trained in the most current techniques in materials science, and be prepared for careers in scientific research. In addition, the PI will continue to run a highly successful summer program to introduce and encourage talented high school students to pursue careers in science and engineering.TechnicalThis award by the Biomaterials program in the Division of Materials Research to University of Pennsylvania is to engineer an amphiphilic plant protein, oleosin, to make targeted, responsive nanocarriers for drug delivery and imaging. Because oleosin is made recombinantly, we can embed designer functionality within these vesicles using the tools of molecular biology. The resulting investigation will lead to a new class of responsive, bio-inspired materials with enormous flexibility for targeted delivery. The PI hypothesize that large stretches of oleosin can be replaced with domains from other proteins, preserving the amphilicity and self-assembly of the molecules, but allowing the design of new materials. One strategy will be to embed protease cleavable domains into materials that allow for environmental proteases to trigger the binding of nano-materials, or the release of drugs they are carrying after binding. A second strategy will be to incorporate domains from human intrinsically disordered proteins into oleosin, which will allow us to make humanized oleosins. The PI will study how the length, number and type of IDP affects the assembly of the nanocarrier and reduces its immunogenicity. The PI will demonstrate how these materials can be used to deliver drugs specifically to inflammatory sites using activated endothelial cells in a flow chamber, targeting the endothelial surface molecule E-selectin. In the process, graduate students will be educate in cutting edge methods for making and testing the activity of recombinant proteins, and introduce high school students to research at the university level and encourage them to pursue careers in science and engineering.

材料研究的一个目标是制造响应性、生物相容性的材料，这些材料可以对环境条件做出独特的反应，也可以针对身体的特定部位。能够特异性靶向疾病部位的载体的开发将提高治疗的功效并减少全身递送的药物的毒副作用。纳米材料，如球形胶束和囊泡，可用于携带大的药物和成像剂的有效载荷。对于靶向药物递送的所有承诺，有相对的纳米材料提供稳健的靶向递送，同时对环境条件作出反应。为了满足这一重大需求，PI的目标是制造一类纳米载体，由一种称为油质蛋白的天然植物蛋白制成，可以靶向特定位点，仅在特定位置开启药物递送，并具有降低的免疫原性。PI将使用重组生物技术将反应域引入蛋白质中，并使用内衬有内皮细胞的流动室演示由蛋白质制成的载体如何与炎症部位结合，内皮细胞是血管的细胞。这项工作也将影响PI实验室培训的学生的生活。从事该项目的研究生将接受材料科学最新技术的培训，并为从事科学研究做好准备。此外，PI还将继续举办一个非常成功的暑期项目，以介绍和鼓励有才华的高中生从事科学和工程方面的职业。技术宾夕法尼亚大学材料研究部生物材料项目的这一奖项是设计一种两亲性植物蛋白，油质蛋白，以制造用于药物输送和成像的靶向，响应性纳米载体。因为油质蛋白是重组的，我们可以使用分子生物学的工具将设计师的功能嵌入这些囊泡中。由此产生的调查将导致一类新的响应性，生物启发材料具有巨大的灵活性，可用于靶向输送。PI假设大部分油质蛋白可以被其他蛋白质的结构域取代，保留分子的两亲性和自组装，但允许设计新材料。一种策略是将蛋白酶可切割结构域嵌入材料中，允许环境蛋白酶触发纳米材料的结合，或在结合后释放它们所携带的药物。第二个策略是将人类内在无序蛋白的结构域整合到油质蛋白中，这将使我们能够制造人源化油质蛋白。PI将研究IDP的长度、数量和类型如何影响纳米载体的组装并降低其免疫原性。PI将演示如何使用这些材料在流动室中使用活化的内皮细胞将药物特异性地递送到炎症部位，靶向内皮表面分子E-选择素。在这个过程中，研究生将接受制作和测试重组蛋白活性的尖端方法的教育，并向高中生介绍大学水平的研究，并鼓励他们从事科学和工程职业。