CAREER: Training Diverse Scientists to Design Bionanomaterials for Imaging and Labeling of Therapeutic Stem cells

职业：培训多元化科学家设计用于治疗性干细胞成像和标记的生物纳米材料

• 批准号: 2145427
• 负责人: Marilyn Mackiewicz
• 金额: $ 55.77万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2145427&HistoricalAwards=false
• 关键词: CAREER; Training; Diverse; Scientists; Design

Non-technical abstract: This CAREER award made by the Biomaterials Program in the Division of Materials Research to Oregon State University focuses on nanomaterials research to advance national health. New nanomaterials combine cell-labeling and imaging capabilities to visually track stem-cell-based regenerative medicine therapies longitudinally in real-time via optical coherence tomography (OCT) imaging. The materials from this project will allow researchers to study the migration and survival after transplantation in vivo, capabilities that currently do not exist. Highly reflective nanomaterials improve the resolution of OCT imaging to visualize single cells. The modified coatings on nanoparticle surfaces adhere to therapeutic stem cells, protect nanomaterials from degradation in biological environments, and make them stealthy to evade the immune system. The project develops safe and stable nanomaterials and advances the field by improving understanding of how the properties of the coated nanomaterials influence their stability, cellular uptake, and retention without compromising cell health and function. It also advances the potential of preclinical research by providing new tools for studying the safety and efficacy of therapeutic stem cells. The project will benefit society by addressing convergent challenges in human health and nanomedicine and by providing broadly applicable new materials for (1) diagnostic imaging, (2) drug delivery, and (3) preclinical research tools to advance cell-based therapies for retinal diseases, cancer, and neurodegeneration. The investigator integrates this research with a comprehensive education program to inspire and train the next generation of diverse scientists in bionanomaterials research for nanomedicine. The educational platform comprises an Ignite in STEM research program; enrichment curriculum focused on professional skills; and a course-based research experience that provides K12 and undergraduate students from underserved communities with authentic experiences, transferable skills as chemists, and opportunities to reveal the hidden curriculum needed to build strong scientific and professional identities for retention in STEM.Technical abstract:Current methods for evaluating cell-based therapies, i.e., gaining insights into cell migration, integration, and survival after transplantation rely on histological analysis of tissues post-mortem. This approach is costly and requires that many animals be sacrificed. The ability to track these cells longitudinally in vivo is hampered by the inability to identify transplanted cells with current imaging methods. This NSF CAREER award is focused on studying how hybrid membrane-coated nanomaterials (HMNPs) may be optimized as optical coherence tomography (OCT) contrast agents and nanolabels for cell-based therapies, uniquely advancing the capabilities of preclinical studies focused on cell transplantation. Creating membranes to coat nanomaterials that give them “stealth” abilities to evade the immune system represents a frontline nanotechnology challenge in imaging, diagnostic, and drug delivery. The design rules for these coatings in imaging cell-based therapies remain unknown. While prior work shows that membrane-based nanoparticles improve biocompatibility and drug delivery, the ability to use HMNPs to label and visualize transplanted cells using OCT, as this project aims to do, has not yet been realized. The first aim of the project focuses on the synthesis and characterization of HMNPs with high scattering efficiency and reflectance for OCT imaging and membrane architectures with ligands on the HMNPs that attach extracellularly or intracellularly to cells. The second focuses on understanding how the size, shape, and surface chemistry of HMNPs influence their ability to engage and facilitate their cellular uptake and retention. The third focuses on understanding how the structural features of HMNPs and symbiotic cell-labeling influence their reflectance properties and OCT contrast. Together these aims advance fundamental knowledge of HMNPs as preclinical tools to improve the study of cell-based therapies. This project integrates research and professional development skills to increase the number of diverse scientists in STEM by (a) creating a strong outreach program to engage and connect high school STEM students with nanomaterials research, (b) implementing a programmatic enrichment arc in the chemistry majors to hardwire success in chemistry with transferable asset-based skills, and (c) creating a Course-based Undergraduate Research Experience (CURE) focused on interfacing nanomaterials with biological systems.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.

非技术摘要：生物材料计划在俄勒冈州立大学材料研究部颁发的职业奖，重点介绍纳米材料研究，以促进国家健康。新的纳米材料结合了细胞标记和成像功能，可通过光学相干断层扫描（OCT）成像实时地实时纵向跟踪基于干细胞的再生医学疗法。该项目的材料将使研究人员能够研究体内移植后的迁移和生存，目前不存在的能力。高度反射的纳米材料改善了OCT成像的分辨率以可视化单细胞。纳米颗粒表面的改性涂层粘附在热干细胞上，保护纳米材料免受生物学环境中的降解，并使它们隐身逃避免疫系统。该项目通过提高对涂层纳米材料的特性如何影响其稳定性，细胞摄取和保留而不会损害细胞健康和功能的情况，从而开发出安全稳定的纳米材料并提高了该领域的发展。它还通过提供研究治疗干细胞的安全性和有效性的新工具来提高临床前研究的潜力。该项目将通过应对人类健康和纳米医学的收敛挑战，并通过为（1）（1）诊断成像，（2）药物输送以及（3）临床前研究工具提供广泛适用的新材料来使社会受益。研究人员将这项研究与综合教育计划相结合，旨在激发和培训纳米医学的生物学材料研究中的下一代科学家。教育平台完成了STEM研究计划的点火。丰富的课程专注于专业技能；以及提供基于课程的研究经验，该经验为来自服务不足社区的K12和本科生提供了真实的经验，作为化学家的转移技能转移了技能，以及揭示建立坚固的科学和专业身份所需的隐藏的流行术语，以确保STEM的保留率。技术摘要：当前的方法，用于评估基于细胞的迁移和迁移的基于细胞的迁移，在迁移后，依次迁移，并将其整合到迁移中，并将其整合到迁移中，并将其置于整合，并将其置于整合，并将其置于临床上，并将其整体置于迁移状态。验尸。这种方法是昂贵的，要求牺牲许多动物。无法通过当前成像方法识别移植的细胞来阻碍体内纵向跟踪这些细胞的能力。该NSF职业奖的重点是研究如何优化杂交膜涂层的纳米材料（HMNP），可作为光学相干断层扫描（OCT）对比剂和基于细胞的疗法的纳米标准，从而唯一地推进了促链细胞研究的能力，这些功能集中在细胞移植上。创建为纳米材料覆盖的机制，使它们具有“隐形”能力以逃避免疫学系统，这代表了成像，诊断和药物输送的前线纳米技术挑战。这些涂层在基于成像细胞的疗法中的设计规则仍然未知。虽然先前的工作表明，基于膜的纳米颗粒改善了生物相容性和药物递送，但尚未实现使用HMNP来标记和使用OCT可视化移植细胞的能力，尚未实现。该项目的第一个目的集中于具有高散射效率的HMNP的合成和表征，以及对OCT成像和膜结构的反射率和反射率，并在HMNP上具有配体，这些HMNP在细胞外或细胞内附着于细胞上。第二个重点是了解HMNP的大小，形状和表面化学如何影响其参与和促进其细胞摄取和保留的能力。第三个重点是理解HMNP和共生细胞标记的结构特征如何影响其反射特性和OCT对比度。这些目标共同提高了HMNP作为临床前工具的基本知识，以改善基于细胞的疗法的研究。该项目通过（a）通过（a）创建强大的外展计划，与纳米材料研究一起吸引和连接高中STEM的学生，（​​b）在化学专业中实施纳米材料的弧线，以基于转移的资产的技能和基于课程的不体研究培训（c），（c），（c）在化学专业中实现（c），（c），（c），（C） Systems.本奖反映了NSF的法定使命，并通过使用基金会的知识分子优点和更广泛的影响评估标准来评估被认为是宝贵的支持。

项目成果

Increasing the Efficacy of Gold Nanorod Uptake in Stem Cell-Derived Therapeutic Cells: Implications for Stem Cell Labeling and Optical Coherence Tomography Imaging

• DOI: 10.1021/acsanm.2c00958
• 发表时间: 2022-05
• 期刊: ACS Applied Nano Materials
• 影响因子: 5.9
• 作者: Grant W Marquart;Jonathan Stoddard;Karen Kinnison;F. Zhou;Richard Hugo;R. Ryals;Scott A. Shubert