Toroidal-spiral particles (TSPs) for co-delivery of multiple compounds of different sizes

非技术：该奖项由伊利诺伊大学芝加哥分校材料研究部的生物材料项目颁发，旨在发展对材料科学基础的基本理解，以开发一种基于聚合物的新技术，为脑肿瘤等复杂疾病的局部部位提供鸡尾酒治疗药物。前几代高分子药物递送载体在昂贵药物的包封效率、保护精细蛋白药物的生物利用度、多药独立调节释放谱以获得最佳治疗效果等方面面临着困难的挑战。环形螺旋颗粒（甜甜圈形螺旋颗粒- TSP）通过新型的内部结构和颗粒形成机制和载药机制解决了这些问题。实验和计算结果的视觉吸引力，以及生物医学应用的社会相关性，对被招募进入化学工程的高中生来说是一个自然的吸引力。教育模块的宣传和更广泛的传播将通过以下方式进行：1)直接联系芝加哥的21所高中；2)年度美国化学工程师学会芝加哥分会学生研讨会；3)由首席研究员与芝加哥科学与工业博物馆联合举办的“科学未成年人”学生研讨会。技术：该奖项支持对关键材料科学和功能问题的研究，这些问题需要解锁用于多种药物输送的新型聚合物平台：环形螺旋颗粒（TSP）的技术和社会影响。粒子的环形螺旋（TS）结构通过滴沉降、扩散和交联的竞争动力学自组装。在TSP形成过程中，治疗性蛋白和寡核苷酸等大分子可以被自动夹带到TS通道中，而小分子药物可以预先混合到聚合物滴液中。在凝固成颗粒后，每种化合物通过单独的途径释放，可以独立操纵以达到治疗协同作用。该项目将解决TSP技术的三个主要方面：(1)加强许多进一步的生物医学和生物技术应用，将研究和测量TSP的可调生物降解；(2)独立操作细胞毒性药物与治疗性蛋白质的释放谱，将实验室测量与计算模型相结合，以确定结构-释放关系并优化生物医学应用的结构；(3)体外表征TSP释放的药物的细胞关联和活性将使用脑肿瘤和内皮组织模型细胞系。除了对所涉及的研究生研究助理进行多学科培训，培养本科生研究机会（强调少数族裔学生的参与）和本科工程教育的副产品外，该项目还为芝加哥和6-12年级以及社区大学的学生提供了多种推广和传播途径。

Nontechnical: This award by the Biomaterial program in the Division of Materials Research to University of Illinois Chicago is to develop a basic understanding of the materials-science basis for a new polymer-based technology to deliver a cocktail of therapeutic drugs locally to the sites of complex diseases such as brain tumors. Previous generations of polymeric drug-delivery vehicles have faced difficult challenges in encapsulation efficiency of expensive drugs, protecting the bioavailability of delicate protein drugs, and independent tuning of release profiles of multiple drugs for optimum therapeutic effect. Toroidal-spiral particles (donut shaped spiral particles - TSP) solve these problems via the novel internal structure and mechanism of particle formation and drug loading. The visually appealing nature of the experimental and computational results, as well as the societal relevance of the biomedical applications, represents a natural draw for high school students being recruited into chemical engineering. Publicity for educational modules and broader dissemination will occur through: 1) direct outreach to 21 Chicagoland high schools; 2) the annual American Institute of Chemical Engineers Chicago Section Student Symposium; and 3) "Science Minors" student workshops co-organized by the Principal Investigator and the Chicago Museum of Science and Industry.Technical: This award enables research into key materials - science and functionality issues needed to unlock the technological and societal impact of a new polymeric platform for multi-drug delivery: toroidal-spiral particles (TSP). The toroidal-spiral (TS) structure of the particles is self-assembled through competitive kinetics of drop sedimentation, diffusion, and cross-linking. During the formation of the TSP, macromolecules such as therapeutic proteins and oligonucleotides can be auto-entrained into the TS channel, while a small molecular drug can be pre-blended into the polymer drops. Upon solidification into particles, the release of each compound occurs through a separate pathway and can be manipulated independently to reach therapeutic synergy. This project will address three main, enabling aspects of TSP technology: (1) enhance many further biomedical and biotechnical applications, tunable biodegradation of TSP will be studied and measured; (2) independent manipulation of release profiles of cytotoxic drug versus therapeutic proteins will combine laboratory measurements with computational models to ascertain the structure-release relation and to optimize structures for biomedical applications; and (3) in vitro characterization the cellular association and activity of agents released from TSP will use model cell lines for brain tumors and endothelial tissue. In addition to multidisciplinary training of the graduate research assistants involved, fostering undergraduate research opportunities (emphasizing underrepresented minority student participation) and spin-offs in undergraduate engineering education, this project offers multiple avenues for outreach and dissemination among Chicago and grade 6-12 and community-college students.