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。在包括脂质，水和血红蛋白散射在内的生物组织中常见的分子光线，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，为我们提供了体内的光窗。第一个，第二和第三NIR光学窗口（NIR-I，II和 iii）每个都有优势，从可访问和经济的SI探测器（NIR-I）到还原在NIR-II和III中，散射中的分辨率明显改善。要在组织内部看到，我们需要明亮，光稳定，吸收高度，NIR荧光团。另外，定期临床使用任何对比剂要求它具有生物相容性，并在使用后将其从身体中移除。我们提出了一种新材料综合可调节的生物相容性和可生物降解的半导体QD的开发工作在NIR-I，II或III中进行成像。我们提出了一种新颖的，光学活跃的半导体纳米颗粒，该纳米粒子完全在体内降解进行临床分子成像。无机造影剂（如半导体量子点）（QD）是广泛生物医学研究的重点，但对临床翻译几乎没有希望因为材料包括有毒成分。即使是惰性，看似生物相容性的无机材料金纳米颗粒具有无限期积累在肝脏等组织中的临床风险。这是鲜明的与迄今为止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（离子）用于MRI对比和贫血的治疗。离子中没有重金属避免毒性，而降解和胆汁排泄规避接受的患者可能严重严重的肾脏菌株分子对比剂。此材料概况激发了我们创新的方法来重塑QD的临床光学成像。我们假设仅包含生物构成元素的重金属纳米颗粒将像氧化铁一样被降解和排泄。选择具有小带隙（0.6 eV）的材料表明通过NIR-I，II和III波长态度，吸收和排放将具有大小调节，使得在荧光成像中，通过组织的光渗透范式转移范围。我们将使用计算方法等各种晶体结构的密度功能理论（DFT）建模以预测并优化纳米材料光学特性，以合理设计半导体纳米颗粒的临床纳米颗粒申请。通过这种探索性技术开发R21，我们将合成并表征新颖通过解决功能，毒性和生物积累的当前局限性的半导体纳米颗粒它们在NIR-I，II和III方面的光致发光，生物质量元素的组成以及能力体内降解和排泄。