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CAREER: Viral Capsids as Smart Nanocontainers

职业：作为智能纳米容器的病毒衣壳

基本信息

批准号：
1654405
负责人：
Jeremiah Gassensmith
金额：
$ 50万
依托单位：
University of Texas at Dallas
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-15 至 2022-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1654405&HistoricalAwards=false
关键词：
CAREER Viral Capsids Smart Nanocontainers

项目摘要

Non-technical:This CAREER award by the Biomaterials program in the Division of Materials Research to University of Texas at Dallas is to study protein-based nanoparticles using non-infectious and non-toxic virus capsids as scaffolding materials for possible drug delivery applications. Nanoparticle-based drug delivery systems have traditionally focused on using nanoparticles derived from metals, silica, polymers, etc. However, some of these materials have encountered roadblocks in their applications. For instance, nanoparticles based on inorganic and polymeric materials typically take a long time in clearing by the body, and possible accumulation in different organs. One possible solution is to make nanoparticles from proteins using non-infectious and non-toxic virus particles as a scaffolding. Conceptually, viruses are ideal for drug delivery system as they have been evolutionarily endowed with all the resources and properties needed to deliver a cargo to specific cells. However, one of the issues holding back in the use of protein-based nanoparticles for drug delivery is the lack of synthetic chemistries under conditions that don't cause unfolding or a denaturation of the proteins of the virus particles during their preparation. One of the thrusts of this proposal is in developing several new reaction methods and building a tool kit for future applications. These new reactions would enable to look at new approaches for drug release from protein-based nanoparticles, including the use of external trigger sources like pulsed laser light. To accomplish this, this project will functionalize the protein nanoparticles with 'photo-thermal antennae' that when struck by the appropriate wavelength of light, will result in the rupture of the capsids and release of their contents (cargo, drugs, etc.) into the cell. An important benefit of this research is that this study is multidisciplinary in nature, and readily lends itself to creating a collaborative environment for student teaching and training. These efforts will be harnessed by giving these students opportunities in creating a web-based comics program, which are expected not only to educate, but also entertain school-aged K-12 children and their parents by telling stories on how nanomaterials interact with the body, and how they could help bring about future drug delivery systems for many biomedical applications. Technical: The main objective of this CAREER award is to synthesize thermally responsive protein-based nanoscopic molecular drug delivery system prepared from virus derived nanoparticles that are non-infectious and non-toxic. Many of the current approaches for releasing contents of nanoparticles - either macromolecular or small molecule - depend on exploiting the cellular environment. The significant part of this award is to expand the variety and scope of reactions available for the functionalization of protein-based nanoparticles from virus-like particles QB (VLPs QB). Additionally, this award will study novel approaches in seeking the development of a method to permit cargo release using external sources of radiation - in particular optical radiation. To these ends, this project will focus on two objectives: 1) using a virus-like particles derived from QB as a model, this award will develop bioconjugation chemistries focusing on the disulfide groups found in viral capsid surfaces without significantly undermining the thermal stability of viral particle; and 2) introducing photothermally active receptors (antennae) on the surface of the proteinaceous surface of QB virus particles, and these modified viral particles when exposed to pulsed laser irradiation will cause rapid heating and cooling of the nano carriers resulting in the ruptue of the particles, and this in turn will result in the release of cargo/drug stored inside the VLP. This project, in addition, will demonstrate concurrent bilayer membrane disruption with cargo release as an alternate approach to escape from endosome capture, which in general would result in the degradation of the cargo. The students working in this project, which combines biochemical, physical, and synthetic chemistry, will gain experience and interdisciplinary learning, and these students will be engaging in creating high quality on-line and freely available science oriented and web-based comic strips aimed at K-12 students. These comic strips will be used to promote scientific literacy, and to encourage students and their parents to engage and discuss the ideas and concepts emerging from contemporary research. To that end, the project will take advantage of the unique diversity available at the campus to create multi-lingual comics to engage people from all over the world in the research that is being funded through this award.

非技术：该职业奖由德克萨斯大学达拉斯分校材料研究部生物材料项目颁发，旨在研究基于蛋白质的纳米颗粒，使用非传染性和无毒的病毒衣壳作为支架材料，用于可能的药物输送应用。基于纳米颗粒的药物递送系统传统上主要使用来自金属、二氧化硅、聚合物等的纳米颗粒。然而，其中一些材料在应用中遇到了障碍。例如，基于无机和聚合物材料的纳米颗粒通常需要很长时间才能被人体清除，并可能在不同器官中积累。一种可能的解决方案是利用非传染性和无毒的病毒颗粒作为支架，从蛋白质中制造纳米颗粒。从概念上讲，病毒是理想的药物输送系统，因为它们在进化中被赋予了将货物输送到特定细胞所需的所有资源和特性。然而，阻碍以蛋白质为基础的纳米颗粒用于药物递送的一个问题是，在制备病毒颗粒的过程中，在不导致病毒颗粒的蛋白质展开或变性的条件下，缺乏合成化学物质。这项提议的重点之一是开发几种新的反应方法，并为未来的应用建立一个工具包。这些新的反应将使人们看到从基于蛋白质的纳米颗粒释放药物的新方法，包括使用脉冲激光等外部触发源。为了实现这一目标，该项目将用“光热天线”使蛋白质纳米粒子功能化，当被适当波长的光照射时，它将导致衣壳破裂，并将其内容物（货物、药物等）释放到细胞中。这项研究的一个重要好处是，这项研究本质上是多学科的，很容易为学生的教学和培训创造一个协作的环境。这些努力将通过给这些学生机会创建一个基于网络的漫画项目来加以利用，该项目不仅可以教育，而且还可以通过讲述纳米材料如何与身体相互作用的故事来娱乐学龄的K-12儿童和他们的父母，以及它们如何有助于为许多生物医学应用带来未来的药物输送系统。技术方面：该职业奖的主要目标是合成由病毒衍生的纳米颗粒制备的热反应性蛋白质纳米级分子药物传递系统，该系统具有非传染性和无毒性。目前许多释放纳米颗粒内容物的方法——无论是大分子还是小分子——都依赖于利用细胞环境。该奖项的重要部分是扩大了从病毒样颗粒QB （VLPs QB）中获得基于蛋白质的纳米颗粒功能化的反应的种类和范围。此外，该合同将研究新的方法，以寻求开发一种允许使用外部辐射源，特别是光辐射释放货物的方法。为此，该项目将重点关注两个目标：1)使用来自QB的病毒样颗粒作为模型，该奖项将开发生物偶联化学，重点关注病毒衣壳表面发现的二硫基团，而不会显著破坏病毒颗粒的热稳定性；2)在QB病毒颗粒的蛋白质表面引入光热活性受体（天线），这些修饰的病毒颗粒在脉冲激光照射下会使纳米载体快速加热和冷却，导致颗粒破裂，从而导致储存在VLP内的货物/药物释放。此外，该项目还将展示同时发生的双层膜破坏和货物释放，作为逃避核内体捕获的另一种方法，这通常会导致货物的降解。在这个结合生化、物理和合成化学的项目中工作的学生将获得经验和跨学科的学习，这些学生将致力于为K-12学生创造高质量的在线和免费的科学导向和基于网络的连环漫画。这些连环画将用于提高科学素养，并鼓励学生和家长参与和讨论当代研究中出现的想法和概念。为此，该项目将利用校园独特的多样性，创作多语言漫画，吸引来自世界各地的人们参与这项由该奖项资助的研究。

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Supramolecular and biomacromolecular enhancement of metal-free magnetic resonance imaging contrast agents

DOI：
10.1039/c9sc05510j
发表时间：
2020-02-28
期刊：
CHEMICAL SCIENCE
影响因子：
8.4
作者：
Lee, Hamilton;Shahrivarkevishahi, Arezoo;Gassensmith, Jeremiah J.
通讯作者：
Gassensmith, Jeremiah J.

PhotothermalPhage: A Virus-Based Photothermal Therapeutic Agent

光热噬菌体：一种基于病毒的光热治疗剂

DOI：
10.1021/jacs.1c05090
发表时间：
2021
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Shahrivarkevishahi, Arezoo;Luzuriaga, Michael A.;Herbert, Fabian C.;Tumac, Alisia C.;Brohlin, Olivia R.;Wijesundara, Yalini H.;Adlooru, Abhinay V.;Benjamin, Candace;Lee, Hamilton;Parsamian, Perouza
通讯作者：
Parsamian, Perouza

Supramolecular Encapsulation of Small-Ultrared Fluorescent Proteins in Virus-Like Nanoparticles for Noninvasive In Vivo Imaging Agents