Multiplexed Imaging in the Near Infrared with Indium Phosphide Quantum Shells

使用磷化铟量子壳进行近红外多重成像

基本信息

批准号：
10224242
负责人：
Allison Marie Dennis
金额：
$ 46.2万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224242
关键词：
Address Animal Model Animals Area Arsenic Benchmarking Binding Biodistribution Biological Biological Assay Biological Markers Biological Process Biomedical Research Blood Circulation Blood Circulation Time Boston Cadmium Cell surface Chemistry Color Communities Contrast Media Development Development Plans Diagnostic Dyes Effectiveness Elements Ensure Equipment Event Fluorescence Formulation Future Geometry Gold Health Heavy Metals Hemoglobin Image Image Enhancement In Vitro Investments Lead Light Lipids Malignant Neoplasms Mercury Methods Micelles Microscopy Molecular Probes Monitor Nonionizing Radiation Operative Surgical Procedures Optics Penetration Performance Photons Pilot Projects Property Proteins Protocols documentation Quantum Dots Resolution Resources Semiconductors Skin Structure Teacher Professional Development Techniques Testing Time Tissue Model Tissues Toxic effect Tumor Markers Universities Visualization Water absorption animal imaging base bioimaging biomaterial compatibility cancer imaging cell type clinical optical imaging contrast imaging cost cytotoxicity design experience experimental study faculty mentor fluorescence imaging fluorophore imaging agent imaging modality imaging probe imaging study improved in vivo in vivo Model in vivo imaging indium phosphide innovation malignant breast neoplasm millimeter molecular imaging molecular phenotype mouse model multiphoton imaging multiphoton microscopy multiplexed imaging nanomaterials nanoparticle novel particle pre-clinical quantum sensor soft tissue success targeted imaging technology development tissue phantom tool tumor tumor growth tumor xenograft

项目摘要

Project Summary/Abstract Fluorescence has significant potential for biomedical imaging applications because of the relatively low cost of imaging equipment, the nominal toxicity of non-ionizing radiation (i.e., light), the potential for molecular imaging using target-specific contrast agents, and the prospect of multiplexed imaging using discretely colored fluorophores. Molecules common in biological tissues including lipids, water, and hemoglobin scatter and absorb light, rendering tissue opaque to visible wavelengths, but longer, near infrared (NIR) wavelengths penetrate deeper, giving us an optical window into the body. To see inside a tissue, we require bright, photostable, highly absorbing, NIR fluorophores. Despite exceptional results in vitro, we can improve on the in vivo performance of organic dyes, fluorescent proteins, and traditional semiconductor quantum dots (QDs), which are typically dim, toxic, not red enough, or all of the above. We have created a material that literally flips a quantum dot inside out to make a quantum shell (QS) comprised of non-toxic elements (In, P, Se, Zn, S) that is tunable from 500 – 900 nm. Because InP absorbs more efficiently than CdSe, these materials are brighter than previous materials with a smaller size, while emitting in the NIR and reducing toxicity. We propose a technology development plan that would enable us to refine the structural and optical properties of these particles to generate a brightness-matched palette of fluorophores to enable multiplexing in deep tissue. We will deploy these particles in widefield imaging and multiphoton microscopy (MPM) experiments to first objectively quantify and then demonstrate the optical superiority of these probes. After evaluating the in vitro and in vivo biocompatibility of various formulations of water-soluble QSs, we will use targeted and untargeted QSs together for dual probe imaging of cell surface biomarkers to selectively highlight a xenograft tumor. In addition to widefield imaging, we will objectively evaluate the MPM contrast of the QSs. The exceptionally high absorptivity of the particles ensures high two- and three- photon action cross-sections. We will quantitatively compare the brightness and tissue penetration depth of the InP QSs against other red and NIR fluorophores. Synthetic iterations to the particles will use the unique particle geometry to generate QSs with varying emission colors, but the same brightness. We will compare zwitterionic coatings to our benchmark lipid-PEG coating to try to enhance imaging contrast through longer circulation time and more efficient targeting. The success of this project will yield a rainbow of non-toxic, NIR fluorophores that can be used collectively could transform preclinical molecular imaging.

项目概要/摘要由于成本相对较低，荧光在生物医学成像应用中具有巨大的潜力。成像设备、非电离辐射（即光）的名义毒性、分子成像的潜力使用目标特异性造影剂，以及使用离散颜色的多重成像的前景生物组织中常见的分子（包括脂质、水和血红蛋白）会散射和吸收。光，使组织对可见波长不透明，但更长的近红外 (NIR) 波长可以穿透更深入，为我们提供观察身体内部的光学窗口，我们需要明亮、耐光、高度的光。尽管在体外取得了出色的结果，但我们可以改进其体内性能。有机染料、荧光蛋白和传统的半导体量子点（QD），它们通常是暗淡的，有毒、不够红或以上所有情况我们已经创造了一种可以将量子点翻转的材料。制作由无毒元素（In、P、Se、Zn、S）组成的量子壳 (QS)，其可调范围为 500 – 900 由于 InP 的吸收效率比 CdSe 更高，因此这些材料比以前的材料更亮。我们提出了一项技术开发计划，该计划可以实现更小的尺寸，同时在近红外范围内发射并降低毒性。将使我们能够改进这些粒子的结构和光学特性，以生成亮度匹配的我们将在宽场成像中部署这些荧光团调色板，以实现深层组织的多重检测。和多光子显微镜（MPM）实验，首先客观量化，然后证明光学在评估了各种制剂的体外和体内生物相容性之后。水溶性QS，我们将结合使用靶向和非靶向QS进行细胞表面的双探针成像选择性突出异种移植肿瘤的生物标志物除了宽场成像外，我们还将客观评估。 QS 的 MPM 对比度极高，可确保高二阶和三阶粒子的吸收率。我们将定量比较光子作用横截面的亮度和组织穿透深度。 InP QS 与其他红色和近红外荧光团的合成迭代将使用独特的粒子。生成具有不同发射颜色但相同亮度的 QS 的几何结构我们将比较两性离子。涂层与我们的基准脂质 PEG 涂层相结合，尝试通过更长的循环时间来增强成像对比度该项目的成功将产生一系列无毒的近红外荧光团。可以共同使用可以改变临床前分子成像。