Multiplexed Imaging in the Near Infrared with Indium Phosphide Quantum Shells

项目摘要/摘要 由于相对较低的成本，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)的标称毒性，分子成像的潜力 使用目标特定的造影剂，以及使用离散颜色的多路成像的前景 荧光团。生物组织中常见的分子，包括脂类、水和血红蛋白，可以分散和吸收。 光，使组织不透明到可见光波长，但更长的近红外(NIR)波长可以穿透 更深的地方，给了我们一个了解身体的光学窗口。要看到纸巾的内部，我们需要明亮、耐光性好、高度 吸收，近红外荧光团。尽管在体外取得了特殊的结果，但我们可以改进其体内表现。 有机染料、荧光蛋白质和传统半导体量子点(QD)，它们通常是暗淡的， 有毒，不够红，或者以上所有的。我们已经创造了一种材料，可以将量子点从里到外翻转 制作由无毒元素(In、P、Se、Zn、S)组成的量子壳(QS)，可在500-900之间调节 NM。由于InP比CdSe更有效地吸收，这些材料比以前的材料更明亮 更小的尺寸，同时在近红外中发射并降低毒性。我们提出了一个技术发展计划， 将使我们能够改进这些粒子的结构和光学属性，以产生与亮度匹配的 可在深层组织中实现多路传输的荧光团调色板。我们将在广域成像中部署这些粒子 和多光子显微镜(MPM)实验首先要客观量化，然后再演示光学 这些探头的优越性。在评价了不同剂型的体内外生物相容性后 水溶性QSS，我们将使用靶向和非靶向QSS一起进行细胞表面的双探针成像 选择性地突出异种移植瘤的生物标记物。除了广域成像，我们还将客观地评估 QSS的MPM对比度。颗粒的异常高的吸收率确保了高的二和三- 光子作用横截面。我们将定量比较这些组织的亮度和穿透深度。 INP QSS与其他红色和近红外荧光团的对比。粒子的合成迭代将使用唯一的粒子 几何图形可生成具有不同发射颜色但亮度相同的QSS。我们将会比较zwitterion 我们的基准脂质-聚乙二醇涂层，试图通过更长的循环时间来增强成像对比度 以及更有效的目标定位。该项目的成功将产生无毒、近红外荧光团的彩虹 可以共同使用可以改变临床前分子成像。

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.