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

肽是化学上连接的短链氨基酸。肽基材料是非常有前途的癌症药物载体，因为它们提供了提高抗癌功效的潜力，同时减少了癌症药物成分的副作用。这些材料还具有易于制造，潜在的生物相容性和可调的化学性质。然而，肽基材料作为抗癌药物纳米载体的应用面临着重大挑战。该项目的目标是建立在有希望的初步工作与特定肽（环二组氨酸或环hh）。研究人员将使用计算和实验方法来开发新型的“智能”肽基纳米材料，用于递送抗癌药物表柔比星。这种纳米载体的设计过程将基于多肽自组装机制，从而提高治疗性能。该项目还涉及教育活动，以促进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层面。研究小组还将参与向代表性不足的高中生提供服务。本课题的研究目标是开发一种新型的抗癌药物纳米载体。研究小组将进行计算和实验研究，以检验环二组氨酸是否可以作为“通用”纳米载体自（核/壳）包封不同结构和物理化学性质的抗癌药物，以及不同的加工条件对药物自包封的影响。研究人员还将设计多肽纳米载体，在多肽-药物混合排列中结合增强的荧光和对癌症药物的高结合亲和力。最后，该团队将通过与cxcr4靶向肽的共组装，将最有前途的纳米载体转化为能够靶向癌细胞的智能药物纳米载体。由此产生的肽材料有望成为一种可行的替代方案，并有望成为递送癌症药物的途径，它将易于制造与一系列功能相结合，包括增强荧光以监测药物释放、优化药物封装和改进癌细胞靶向。除了非常有前途的新材料外，该研究项目还将创建一个计算协议，为设计作为抗癌药物纳米载体的功能性肽材料提供革命性的新方法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.