Biodegradable and Biocompatible Semiconductor Nanoparticles for Deep Tissue Imaging

用于深层组织成像的可生物降解和生物相容性半导体纳米颗粒

基本信息

批准号：
9979273
负责人：
Allison Marie Dennis
金额：
$ 24.75万
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：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9979273
关键词：
Address Alloys Anemia Animals Arsenic Bile fluid Biliary Biodegradation Biodistribution Biological Biomedical Research Clinical Color Computer Models Contrast Media Copper Coupled Crystallization Development Diagnostic Diagnostic Imaging Disease Elements Encapsulated Equipment Evolution Excretory function Exhibits FDA approved Fluorescence Goals Gold Health Heavy Metals Hemoglobin Histology Human Image In Vitro Inbred BALB C Mice Iron Kidney Lead Light Lipids Liver Magnetic Resonance Imaging Measures Mercury Metabolic Pathway Methods Micelles Modality Modeling Molecular Monitor Nonionizing Radiation Operative Surgical Procedures Optics Organ Weight Oxides Pathway interactions Patients Penetration Property Protocols documentation Quantum Dots Resolution Semiconductors Serum Skin Spleen Structure Sulfides Sulfur Surface Testing Time Tissue imaging Tissues Toxic effect Water Weight Zinc absorption base bioaccumulation bioimaging biomaterial compatibility clinical application clinical development clinical imaging clinical optical imaging clinical risk clinical translation cost cytotoxicity density design detector experience fluorescence imaging fluorophore imaging agent improved in vivo in vivo evaluation in vivo imaging innovation iron oxide iron oxide nanoparticle molecular imaging multiplexed imaging nanoGold nanomaterials nanoparticle novel particle photoacoustic imaging pre-clinical prevent quantum sensor side effect targeted treatment technology development theories tool tumor zinc sulfide

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 optical windows into the body. The first, second, and third NIR optical windows (NIR-I, II, and III) each have advantages ranging from use with accessible and economical Si detectors (NIR-I) to a reduction in scattering, and thus a marked improvement in resolution, in the NIR-II and III. To see inside a tissue, we require bright, photostable, highly absorbing, NIR fluorophores. In addition, the regular clinical use of any contrast agent requires that it is biocompatible and removed from the body following its use. We propose a new materials development effort to synthesize biocompatible and biodegradable semiconductor QDs that can be tuned for imaging in the NIR-I, II, or III. We propose a novel, optically active semiconductor nanoparticle that fully degrades in vivo for clinical molecular imaging. Inorganic contrast agents like semiconductor quantum dots (QDs) have been the focus of extensive biomedical research, but hold little promise for clinical translation because the materials comprise toxic constituents. Even inert, seemingly biocompatible inorganic materials like gold nanoparticles carry the clinical risk of accumulating indefinitely in tissues like the liver. This is in stark contrast to the only inorganic nanoparticle that has been FDA-approved to date: iron oxide nanoparticles (IONs) for MRI contrast and the treatment of anemia. The absence of heavy metals in IONs avoids toxicity, while degradation and bile excretion circumvent the potentially severe kidney strain experienced by patients receiving molecular contrast agents. This material profile inspires our innovative approach to reinventing QDs for clinical optical imaging. We hypothesize that heavy metal-free nanoparticles comprising only bioessential elements will be degraded and excreted just like iron oxide. The choice of a material with a small bandgap (0.6 eV) indicates that the absorption and emission will be size-tunable through NIR-I, II, and III wavelength regimes, enabling paradigm shifting levels of light penetration through tissues and clarity in fluorescence imaging. We will use computational approaches like density functional theory (DFT) modeling of various crystal structures to predict and optimize nanomaterial optical properties to rationally design semiconductor nanoparticles for clinical applications. Through this Exploratory Technology Development R21, we will synthesize and characterize novel semiconductor nanoparticles that address current limitations in function, toxicity, and bioaccumulation through their photoluminescence in the NIR-I, II, and III regimes, composition of bioessential elements, and capacity for in vivo degradation and excretion.

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荧光团。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，为我们提供了进入身体的光学窗口。第一、第二和第三近红外光学窗口（NIR-I、II 和 III) 每种方法都有优点，从使用方便且经济的硅探测器 (NIR-I) 到减少 NIR-II 和 III 中的散射，从而显着提高了分辨率。要查看组织内部，我们需要明亮、光稳定、高吸收性、近红外荧光团。此外，临床上定期使用任何造影剂要求它具有生物相容性，并在使用后从体内清除。我们提出了一种新材料开发工作合成生物相容性和可生物降解的半导体量子点，可以调整 NIR-I、II 或 III 中的成像。我们提出了一种新颖的光学活性半导体纳米粒子，它完全在体内降解用于临床分子成像。半导体量子点等无机造影剂（量子点）一直是广泛生物医学研究的焦点，但临床转化前景渺茫因为这些材料含有有毒成分。即使是惰性的、看似生物相容的无机材料，如金纳米颗粒具有在肝脏等组织中无限期积累的临床风险。这是赤裸裸的与迄今为止 FDA 批准的唯一无机纳米颗粒形成鲜明对比：氧化铁纳米颗粒 (ION) 用于 MRI 对比和贫血治疗。离子中不含重金属，避免了毒性，同时降解和胆汁排泄避免了接受治疗的患者可能经历的严重肾损伤分子造影剂。这种材料特性激发了我们重新发明临床量子点的创新方法光学成像。我们假设仅包含生物必需元素的无重金属纳米粒子将像氧化铁一样被降解和排出体外。选择带隙较小 (0.6 eV) 的材料表明吸收和发射将通过 NIR-I、II 和 III 波长范围进行尺寸可调，从而使光穿透组织的水平和荧光成像清晰度的范式转变。我们将使用密度泛函理论 (DFT) 等计算方法对各种晶体结构进行建模以进行预测并优化纳米材料的光学特性，合理设计用于临床的半导体纳米颗粒应用程序。通过这个探索性技术开发 R21，我们将合成和表征新颖的半导体纳米粒子，通过以下方式解决当前功能、毒性和生物累积方面的限制它们在 NIR-I、II 和 III 范围内的光致发光、生物必需元素的组成以及体内降解和排泄。