CAREER: Experimental and Theoretical Studies to Develop Complex Biomaterials

职业：开发复杂生物材料的实验和理论研究

• 批准号: 1941731
• 负责人: Martin Conda-Sheridan
• 金额: $ 56.74万
• 依托单位: University of Nebraska Medical Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1941731&HistoricalAwards=false
• 关键词: CAREER; Experimental; Theoretical; Studies; Develop

Dr. Martin Conda-Sheridan and his lab aim to merge material sciences and medicinal chemistry to create tiny materials (nanostructures) to advance science and improve human health. Their goal is to create “on-demand” nanotechnologies tailored to industrial or patient needs. Their first objective is to create two types of nanostructures: those sensitive to different conditions, and those resistant to the environment to meet the needs of the chemical and pharmaceutical industries.Their second objective is to develop computer software that will allow scientists and clinicians to predict the shape and behavior of nanostructures when placed in different environments. Their third objective is to create nanostructures responsive to free radicals, which are linked to aging, illness, and oxidative stress. This can evolve into responsive therapies for health conditions associated with inflammation – including cancer. In summary, Dr. Conda-Sheridan and his team propose to prepare biocompatible nanostructures to develop responsive, on-demand treatments. If successful, a physician may someday consult a computer program to foresee which nanostructure(s) would best treat a health condition. In addition, the team will develop educational activities geared towards students and the general public, seeking to increase the basic understanding of nanotechnology. Wikipedia pages and instructional videos will be translated into several languages in hopes of reaching a wide audience of science enthusiasts. The goal is to teach and share the findings of this project with the wider world, inspiring a new generation of material scientists and engineers working in nanotechnology. Technical AbstractThe design of smart, self-assembling nanostructures with easy to modify properties is a thriving new field that can revolutionize material science, engineering, and chemistry. The long-term goal of this project is to create multifunctional nanostructures that possess tunable properties and are responsive to external stimuli. To achieve this final goal, this project is divided into three objectives. The First Objective will focus on tuning intra- and inter-molecular forces to modify properties at the supramolecular level. This will permit the control of the morphology and physicochemical properties of the nanomaterials. The Second Objective will focus on developing theoretical tools (based in statistical mechanics) that can be used to predict supramolecular shape from the self-assembling molecules. This new software will be used to design novel nanostructures. The Third Objective seeks to prepare stimuli responsive nanomaterials. This will lead to nanostructures that can release selected molecules on demand and at various rates by the action of reactive oxygen species. This research will generate new biomaterials that are composed of diverse chemical functionalities with distinct pKas, hydrogen bonding potential, size, spatial orientation, and stereochemistry. It is expected these new biomaterials can lead to smart nanostructures that can adjust their behavior based on pH, salt concentration, temperature etc. The ability to design and tune material properties and molecular release with the aid of theoretical models and by the simple exchange of building blocks can lead to breakthroughs in material science, engineering, and medicine. In addition, this research will support educational activities geared towards high school, undergraduate and graduate students in a variety of science disciplines as well as the general public to increase nanotechnology literacy. Key concepts in self-assembly and nanotechnology will be disseminated by two primary teaching activities: (1) editing and expanding relevant Wikipedia entries, and (2) the creation of educational videos. The educational component will be translated to multiple languages and made available free to the public in order to reach larger audiences across the globe.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Martin Conda-Sheridan博士和他的实验室旨在将材料科学和药物化学结合起来，创造微小材料（纳米结构），以推进科学和改善人类健康。他们的目标是根据工业或病人的需要创造“按需”的纳米技术。他们的第一个目标是创造两种类型的纳米结构：对不同条件敏感的纳米结构和对环境耐受的纳米结构，以满足化学和制药工业的需求。他们的第二个目标是开发计算机软件，使科学家和临床医生能够预测纳米结构在不同环境中的形状和行为。他们的第三个目标是创建对自由基有反应的纳米结构，自由基与衰老，疾病和氧化应激有关。这可以演变成与炎症相关的健康状况的响应疗法-包括癌症。总之，Conda-Sheridan博士和他的团队建议制备生物相容性纳米结构，以开发响应性，按需治疗。如果成功的话，医生可能有一天会咨询计算机程序来预测哪种纳米结构最适合治疗健康状况。此外，该小组将开发面向学生和公众的教育活动，寻求增加对纳米技术的基本了解。维基百科页面和教学视频将被翻译成多种语言，希望能接触到广大的科学爱好者。我们的目标是与更广泛的世界分享这个项目的发现，激励新一代从事纳米技术工作的材料科学家和工程师。技术摘要设计智能的、自组装的、易于修改性质的纳米结构是一个蓬勃发展的新领域，它可以彻底改变材料科学、工程和化学。该项目的长期目标是创建具有可调特性并对外部刺激做出反应的多功能纳米结构。为了实现这一最终目标，本项目分为三个目标。第一个目标将集中在调整分子内和分子间的力量，以修改在超分子水平的性能。 这将允许控制纳米材料的形态和物理化学性质。第二个目标将侧重于开发理论工具（基于统计力学），可用于从自组装分子预测超分子形状。这个新的软件将用于设计新的纳米结构。第三个目标旨在制备刺激响应纳米材料。这将导致纳米结构可以根据需要并通过活性氧的作用以不同的速率释放选定的分子。这项研究将产生新的生物材料，这些材料由不同的化学功能组成，具有不同的pKas，氢键潜力，尺寸，空间取向和立体化学。预计这些新的生物材料可以导致智能纳米结构，可以根据pH值，盐浓度，温度等来调整它们的行为，借助理论模型和简单的积木交换来设计和调整材料特性和分子释放的能力可以导致材料科学，工程和医学的突破。此外，这项研究将支持面向高中，本科和研究生在各种科学学科以及公众的教育活动，以提高纳米技术素养。自组装和纳米技术的关键概念将通过两个主要的教学活动传播：（1）编辑和扩展相关的维基百科条目，以及（2）创建教育视频。 教育部分将被翻译成多种语言，并免费提供给公众，以达到更大的观众在地球仪。这个奖项反映了NSF的法定使命，并已被认为是值得支持的评估使用基金会的知识价值和更广泛的影响审查标准。

项目成果

Conformal Electrodeposition of Antimicrobial Hydrogels Formed by Self‐Assembled Peptide Amphiphiles

• DOI: 10.1002/admi.202300046
• 发表时间: 2023-04
• 期刊: Advanced Materials Interfaces
• 影响因子: 5.4
• 作者: Gervasio Zaldívar;Jiachen Feng;L. Lizarraga;Yafan Yu;L. D. de Campos;K. D. de Oliveira;K. Piepenbrink;Martin Conda-Sheridan;M. Tagliazucchi

Designing peptide amphiphiles as novel antibacterials and antibiotic adjuvants against gram-negative bacteria

• DOI: 10.1016/j.bmc.2023.117481
• 发表时间: 2023-09-28
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY
• 影响因子: 3.5
• 作者: Xing，Huihua;Loya-Perez，Vanessa;de Almeida，Nathalia Rodrigues
• 通讯作者: de Almeida，Nathalia Rodrigues

Urea-Modified Self-Assembling Peptide Amphiphiles That Form Well-Defined Nanostructures and Hydrogels for Biomedical Applications

• DOI: 10.1021/acsabm.2c00158
• 发表时间: 2022-06-02
• 期刊: ACS APPLIED BIO MATERIALS
• 影响因子: 4.7
• 作者: Xing，Huihua;Rodger，Alison;Conda-Sheridan，Martin
• 通讯作者: Conda-Sheridan，Martin