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

• 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
• 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

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 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 三)每一种都有各种优点，从使用方便和经济的硅探测器(NIR-I)到减少 在散射方面，因此在分辨率上有了显著的提高，在NIR-II和III中。要看到组织内部，我们需要 明亮，光稳定，高吸收，近红外荧光团。此外，任何造影剂的临床常规使用 要求它是生物相容的，并在使用后从体内移除。我们提出了一种新材料 合成生物相容和可生物降解的可调半导体量子点的开发工作 在NIR-I、II或III中成像。我们提出了一种新型的、光学活性的半导体纳米粒子，它完全 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)一直是广泛的生物医学研究的焦点，但在临床翻译方面前景渺茫 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 与迄今为止唯一获得FDA批准的无机纳米颗粒形成对比的是：氧化铁纳米颗粒(离子) 用于MRI对比剂和贫血的治疗。离子中不含重金属可避免毒性，而 降解和胆汁排泄绕过了接受移植的患者可能经历的严重的肾脏压力 分子造影剂。这份材料简介启发了我们为临床重新发明量子点的创新方法。 光学成像。我们假设，只包含生物必需元素的无重金属纳米颗粒将 就像氧化铁一样被降解和排泄。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波长制度进行大小可调，从而能够 改变光透过组织的水平和荧光成像的清晰度。我们将使用 各种晶体结构的计算方法，如密度泛函理论(DFT)建模，以预测 优化纳米材料的光学性质，合理设计用于临床的半导体纳米颗粒 申请。通过这次探索性的技术开发R21，我们将合成和表征小说 半导体纳米颗粒，通过以下途径解决目前在功能、毒性和生物积累方面的限制 它们在NIR-I，II和III区的光致发光，生物必需元素的组成，以及 体内降解和排泄。