Growth of Hybrid Polymeric Nanostructures for Enzyme-Free Amplified Protein Imaging

用于无酶放大蛋白质成像的混合聚合物纳米结构的生长

• 批准号: 1802953
• 负责人: Yong Wang
• 金额: $ 31.87万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1802953&HistoricalAwards=false
• 关键词: Growth; Hybrid; Polymeric; Nanostructures; Enzyme

Proteins play essential roles in the body. However, because they have typically are found in low concentration, they can be very challenging to detect. Overcoming this challenge will not advance basic research and greatly improve the quality of diagnosis and the discovery of new therapeutics. The objective of this project is to develop a novel biosensing nanotechnology to amplify the signals of target proteins. The proteins that cannot be detected using traditional methods would be detected with this new technology. Students at different levels will be trained through hands-on research experience. Nationwide underrepresented students through diverse outreach activities at Penn State will be recruited to this program. The new knowledge to be generated through this program will be integrated into the classes offered to undergraduate and graduate students. Moreover, the knowledge will be broadly disseminated through high-profile journal publications and conference presentations. Protein examination is pivotal to virtually all fields related to biomedical sciences and clinical diagnostics as well. However, existing methods for in situ protein imaging and sensing often suffer from problems such as weak signal intensity, pigment/nanoparticle deposition and slow diffusion of bulky agents. The objective of this project is to explore a novel method for enzyme-free signal amplification in protein imaging via in situ growth of biomolecular nanostructures. The success of exploring this new method will address the critical unmet needs faced by existing methods for protein detection. In the proposed new method, each protein target will be represented by a supramolecular imaging nanostructure that carries a large number of fluorophores. Notably, the nanostructure will be grown in situ for imaging without the need of using any enzyme. Thus, it will not only provide signal amplification but also avoid potential enzyme- or nanoparticle-associated problems. The proposed research is designed with three tasks: 1) to understand how the compositions and structures of DNA molecules determine the formation of DNA nanostructures; 2) to synthesize and characterize hybrid DNA-based supramolecular nanostructures; and 3) to evaluate the effectiveness of this method in protein imaging. The accomplishment of this project will make broad impacts. Firstly, it will advance the methodology of protein sensing, benefiting a variety of biological and biomedical research areas that require highly sensitive protein imaging. Secondly, the fundamental understanding of DNA polymerization will provide a knowledge basis for the development of various DNA-based biosensors and materials. Thirdly, as clinical biopsies often have very small volumes, this enzyme-free signal amplification imaging method also holds great potential of improving clinical diagnostics. The broad impacts will be further strengthened by the development of human resources at different levels with active recruitment of nationwide underrepresented students through a diverse array of Penn State outreach programs, the publication of papers in high-profile journals and the dissemination of knowledge through invited seminars and conference presentations.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.

蛋白质在体内起重要作用。但是，由于它们通常以低浓度发现，因此检测到它们可能非常具有挑战性。克服这一挑战将不会提高基础研究，并大大提高诊断质量和新的治疗剂的发现。该项目的目的是开发一种新型的生物传感纳米技术来扩大靶蛋白的信号。该新技术将检测到无法使用传统方法检测的蛋白质。不同级别的学生将通过动手研究经验进行培训。通过宾夕法尼亚州立大学的各种外展活动，全国代表性不足的学生将被招募到该计划。通过该计划生成的新知识将集成到提供给本科生和研究生的课程中。此外，知识将通过备受瞩目的期刊出版物和会议演讲大致传播。蛋白质检查与几乎所有与生物医学科学和临床诊断有关的领域都是关键的。然而，现有的原位蛋白成像和传感的方法通常会遇到诸如信号强度，色素/纳米颗粒沉积和笨重剂的缓慢扩散等问题。该项目的目的是探索一种新的方法，可通过生物分子纳米结构的原位生长在蛋白质成像中进行无酶的信号扩增。探索这种新方法的成功将解决现有方法检测现有方法所面临的关键未满足需求。在提出的新方法中，每个蛋白质靶标将由带有大量荧光团的超分子成像纳米结构表示。值得注意的是，纳米结构将在不需要使用任何酶的情况下进行原位成像。因此，它不仅会提供信号扩增，而且还可以避免潜在的酶或纳米颗粒相关的问题。拟议的研究设计了三个任务：1）了解DNA分子的组成和结构如何确定DNA纳米结构的形成； 2）合成并表征基于杂化DNA的超分子纳米结构； 3）评估该方法在蛋白质成像中的有效性。该项目的完成将产生广泛的影响。首先，它将推进蛋白质感测的方法，从而使需要高度敏感的蛋白质成像的各种生物学和生物医学研究领域受益。其次，对DNA聚合的基本理解将为开发各种基于DNA的生物传感器和材料的发展提供知识基础。第三，由于临床活检通常具有很小的体积，因此这种无酶的信号放大成像方法也具有改善临床诊断的巨大潜力。 The broad impacts will be further strengthened by the development of human resources at different levels with active recruitment of nationwide underrepresented students through a diverse array of Penn State outreach programs, the publication of papers in high-profile journals and the dissemination of knowledge through invited seminars and conference presentations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader影响审查标准。

项目成果

DNA-templated synthesis of biomimetic cell wall for nanoencapsulation and protection of mammalian cells

• DOI: 10.1038/s41467-019-10231-y
• 发表时间: 2019-05
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Peng Shi;Nan Zhao;James Coyne;Yong Wang

Synthetic DNA for Cell‐Surface Engineering

用于细胞表面工程的合成 DNA

• DOI: 10.1002/ange.202010278
• 发表时间: 2021
• 期刊: Angewandte Chemie
• 作者: Shi, Peng;Wang, Yong
• 通讯作者: Wang, Yong