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

• 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
• 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

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.

项目摘要/摘要 荧光具有生物医学成像应用的显着潜力，因为 成像设备，非电离辐射的标称毒性（即光），分子成像的潜力 使用靶标特异性对比剂，以及使用离散颜色的多路复用成像的前景 荧光团。生物组织中常见的分子，包括脂质，水和血红蛋白散射并吸收 光线，使组织不透明到可见的波长，但较长的红外（NIR）波长穿透了 更深入，为我们提供一个光学窗口进入身体。要在组织内部看到，我们需要明亮，光稳定，高度 吸收NIR荧光团。尽管在体外结果出色，但我们可以改善体内性能 有机染料，荧光蛋白和传统的半导体量子点（QD），通常昏暗， 有毒，不够红或上述所有。我们创建了一种材料，可以从内而外翻转一个量子点 制作由无毒元素（in，p，se，Zn，s）组成的量子壳（QS），可从500 - 900中调谐 NM。因为INP比CDSE更有效地吸收，所以这些材料比以前的材料更明亮 尺寸较小，同时在NIR中排放并降低毒性。我们提出了一个技术发展计划 将使我们能够完善这些粒子的结构和光学特性，以产生亮度匹配 荧光团的调色板可以在深组织中多路复用。我们将将这些粒子部署到广场成像中 和多光子显微镜（MPM）实验，首先客观地量化，然后演示光学 这些问题的优势。在评估了各种公式的体外和体内生物相容性之后 水溶性QSS，我们将使用靶向和未靶向的QS一起进行细胞表面的双重探针成像 生物标志物有选择地突出型元素肿瘤。除了广场成像外，我们还将客观地评估 QSS的MPM对比度。极高的颗粒吸收可确保高两个和三 光子动作横截面。我们将定量比较亮度和组织穿透深度 INP QSS针对其他红色和NIR荧光团。粒子的合成迭代将使用独特的粒子 几何形状生成具有不同发射颜色的QSS，但具有相同的亮度。我们将比较zwitterionic 在我们的基准脂质涂层上涂层，以尝试通过更长的循环时间来增强成像对比度 和更有效的目标。该项目的成功将产生无毒的NIR荧光团的彩虹 可以集体使用可以转化临床前分子成像。