NSF-BSF: Computational and Experimental Design of Novel Peptide Nanocarriers for Cancer Drugs

NSF-BSF：用于癌症药物的新型肽纳米载体的计算和实验设计

• 批准号: 2104558
• 负责人: Phanourios Tamamis
• 金额: $ 39.9万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2104558&HistoricalAwards=false
• 关键词: NSF; BSF; Computational; Experimental; Design; NSF; BSF; Computational; Experimental; Design

Peptides are short chains of chemically linked amino acids. Peptide-based materials are highly promising carrier agents for cancer drugs, because they offer the potential to improve anti-cancer efficacy while reducing the side effects of the constituent cancer drugs. These materials also feature ease of fabrication, potential biocompatibility, and tunable chemical properties. There are, however, significant challenges associated with the application of peptide-based materials as cancer drug nanocarriers. The goal of this project is to build on promising initial work with a specific peptide (cyclo-dihistidine or cyclo-HH). The researchers will use computational and experimental methods to develop novel classes of “smart” peptide-based nanomaterials for delivery of the cancer drug, epirubicin. This nanocarrier design process will be based on peptide self-assembly mechanisms that permit improved therapeutic properties. The project also involves educational activities to promote interdisciplinary training of undergraduate and graduate students and to add an international dimension to their research experience. The research team also will be involved in outreach efforts to underrepresented high-school students.The research aim of this project is to develop a novel classes of cancer drug delivery nanocarriers. The research team will pursue computational and experimental studies to examine whether cyclo-dihistidine can serve as a “universal” nanocarrier self-(core/shell) encapsulating cancer drugs of different structural and physicochemical properties and how different processing conditions may affect drug self-encapsulation. The researchers also will design peptide nanocarriers combining enhanced fluorescence and high binding affinity to cancer drugs in mixed peptide-drug arrangements. Finally, the team will transform the most promising nanocarriers into smart drug nanocarriers capable of targeting cancer cells through co-assembly with CXCR4-targeting peptides. The resulting peptide-materials are expected to be a viable alternative and promising route to delivering cancer drugs, fruitfully combining ease of fabrication with a range of capabilities including enhanced fluorescence to enable monitoring of drug release, optimized drug encapsulation, and improved targeting of cancer cells. Apart from highly promising new materials, the research project will create a computational protocol offering transformative new means for the design of functional peptide-materials serving as cancer drug nanocarriers.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.

肽是化学连接的氨基酸的短链。基于肽的材料是癌症药物的高度有希望的载体剂，因为它们具有提高抗癌效率的潜力，同时降低了组成癌药物的副作用。这些材料还具有易于制造，潜在的生物相容性和可调节化学性能。但是，与将基于肽的材料作为癌症纳米载体的应用存在重大挑战。该项目的目的是建立特定肽（Cyclo-Dihistidine或Cyclo-HH）的承诺初始工作。研究人员将使用计算和实验方法来开发新型的基于“智能”肽的纳米材料来递送癌症药物，表蛋白纤维蛋白。该纳米载体设计过程将基于肽自组装机制，该机制允许改善治疗特性。该项目还涉及教育活动，以促进对本科生和研究生的跨学科培训，并为他们的研究经验增加国际维度。研究小组将参与宣传工作，使代表性不足的高中生。该项目的研究目的是开发一种新型的癌症药物输送纳米载体。研究小组将进行计算和实验研究，以检查环丁氨酸是否可以用作“通用”纳米载体自我（核心/外壳），封装了不同结构和物理特性的癌症药物，以及不同的处理条件如何影响药物自我囊化。研究人员还将设计肽纳米载体，结合了混合肽 - 药物排列中癌症药物的增强和高结合亲和力。最后，该团队将将最有前途的纳米载体转变为能够通过与CXCR4靶向肽共组装靶向癌细胞的智能药物纳米载体。预计所得的肽材料将是可行的替代方案和有前途的癌症药物途径，将易于制造的易于制造与一系列能力相结合，包括增强的荧光，从而可以监测药物释放，优化的药物包封以及改善癌细胞的靶向靶向。除了高度有希望的新材料外，该研究项目还将创建一项计算协议，提供用于设计功能性肽材料的新型方法，以癌症药物纳米载体的设计。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查标准来通过评估来通过评估来支持的。