Responsive Hybrid Oleosin Nanomaterials

材料研究的一个目标是制造反应灵敏的、生物相容的材料，这种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发展将提高治疗的疗效，并减少全身输送药物的毒副作用。纳米材料，如球形胶束和囊泡，可用于携带大量有效载荷的药物和显像剂。对于靶向药物递送的所有承诺，有相对的纳米材料，提供强大的，有针对性的递送，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，由一种天然存在的植物蛋白油质制成，它可以靶向特定部位，只在特定部位开启药物输送，并且降低了免疫原性。PI将使用重组生物技术将反应域引入蛋白质，并演示由蛋白质制成的载体如何使用内衬内皮细胞（血管细胞）的流室与炎症部位结合。这项工作还将影响在PI实验室接受培训的学生的生活。从事该项目的研究生将接受材料科学最新技术的培训，为从事科学研究工作做好准备。此外，PI将继续举办一个非常成功的暑期项目，以引进和鼓励有才华的高中生从事科学和工程方面的职业。该奖项由宾夕法尼亚大学材料研究部的生物材料项目授予，旨在设计一种两亲性植物蛋白油质，用于制造靶向性、反应性的纳米载体，用于药物输送和成像。因为油蛋白是重组的，我们可以使用分子生物学的工具在这些囊泡中嵌入设计功能。由此产生的研究将导致一种新型的反应灵敏的，具有巨大灵活性的生物启发材料的目标交付。PI的假设是，大范围的油蛋白可以被其他蛋白质的结构域取代，保留分子的双亲和性和自组装性，但允许设计新材料。一种策略是将蛋白酶可切割区域嵌入到材料中，使环境蛋白酶能够触发纳米材料的结合，或者在结合后释放它们携带的药物。第二种策略是将人类内在无序蛋白质的结构域整合到油蛋白中，这将使我们能够制造人源化的油蛋白。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激活内皮细胞，靶向内皮表面分子e -选择素，将药物特异性地递送到炎症部位。在这个过程中，研究生们将学习制造和测试重组蛋白活性的尖端方法，并将高中学生引入大学水平的研究，鼓励他们从事科学和工程方面的职业。

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.