Biocompatible Graphene Quantum Dots for Noninvasive Near-infrared Bioimaging

用于无创近红外生物成像的生物相容性石墨烯量子点

• 批准号: 10203022
• 负责人: Anton Naumov
• 金额: $ 41.01万
• 依托单位: TEXAS CHRISTIAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203022
• 关键词: Address; Adverse effects; Animal Experimentation; Animal Model; Animal Testing; Animals; Area; Biological; Biological Assay; Biosensing Techniques; Biotechnology; Cell Survival; Cells; Chemicals; Clinical; Complex; Contrast Media; Defect; Development; Diagnosis; Diagnostic; Drug Delivery Systems; Drug Transport; Exhibits; Fluorescence; Fluorescence Microscopy; Future; Glucosamine; Health; Human; Image; Image-Guided Surgery; In Situ; In Vitro; Light; Magnetic Resonance Imaging; Medical Students; Microscopic; Minor; Mus; Natural graphite; Near-infrared optical imaging; Operative Surgical Procedures; Ophthalmology; Optics; Organ; Oxides; Oxygen; Patients; Penetration; Pharmaceutical Preparations; Process; Property; Quantum Dots; Rare Earth Metals; Research; Science; Site; Slice; Structure; System; Techniques; Testing; Therapeutic; Time; Tissue imaging; Tissues; Toxic effect; UV Radiation Exposure; Visible Radiation; Visualization; Work; animal imaging; base; bioimaging; biomaterial compatibility; career; drug testing; feasibility testing; fluorescence imaging; fluorophore; functional group; graphene; image guided; image-guided drug delivery; imaging agent; imaging platform; in vivo; in vivo imaging; in vivo imaging system; infrared microscopy; luminescence; microwave electromagnetic radiation; mouse model; nanomaterials; near infrared dye; novel; oxidation; ozone exposure; physical property; quantum; real-time images; success; targeted treatment; therapeutic evaluation; tool; tumor; undergraduate student; uptake; water solubility

Project Summary/Abstract Near-infrared (NIR) imaging is one of the most rapidly developing perspective techniques in biomedical diagnostics enabling 10 - 100 times deeper tissue imaging than regular visible fluorescence techniques. There is a significant clinical need for such imaging: high-depth CT and MRI imaging strategies are complex and less suitable for low-depth biosensing and intraoperative applications. Furthermore, in animal studies NIR imaging can enable in situ fluorescence tracking of tested therapeutics or tumor visualization inside a living small animal. However, as NIR imaging field is still developing, there is a lack of biocompatible and multifunctional platforms suitable for imaging, sensing and even drug transport highly desired in animal studies. In this project we will develop and test the feasibility of a novel NIR imaging platform based on graphene quantum dots (GQDs) addressing the critical needs of NIR bioimaging: fluorescence in the NIR (above 950 nm) with NIR excitation, high biocompatibility, photostability, and capabilities for drug tracing and in vivo NIR imaging in live animal models. This will be implemented in 3 steps: (1) synthesizing NIR-emissive GQDs via bottom-up and top-down approaches and characterizing their optical and physical properties, (2) testing GQDs for NIR in vitro imaging and assessing their biocompatibility and (3) performing in vivo imaging of GQD NIR fluorescence in live animals as well as ex vivo organ tissue imaging quantifying GQD content in excised organs. We will concomitantly assess potential adverse effects to select non-toxic GQD candidates. Throughout this process a variety of synthesized GQD structures will undergo rigorous 3-step selection for the capabilities of (1) high yield NIR fluorescence, (2) high biocompatibility and NIR imaging in cells, (3) NIR imaging inside a live sedated animal with minimal/no toxicity. The selected GQD candidates will enable in vivo animal testing of therapeutic delivery with noninvasive real-time image tracking reducing the number of animals sacrificed. In a longer term, we expect these GQD platforms to become a basis of the noninvasive NIR in vivo sensing in patients. As a result, the proposed initiative will address several significant areas of biotechnology and its development will ultimately contribute to the improvement of human health.

项目总结/摘要 近红外（NIR）成像是近年来发展最快的透视技术之一， 生物医学诊断，使组织成像比常规可见光成像深10 - 100倍 荧光技术对于这种成像存在显著的临床需求：高深度CT和 MRI成像策略复杂，不太适合低深度生物传感和术中 应用.此外，在动物研究中，NIR成像可以实现原位荧光跟踪 在活体小动物体内进行治疗或肿瘤可视化。然而，作为NIR成像 尽管该领域仍在发展，但缺乏适合于 成像、传感甚至药物运输都是动物研究中非常需要的。 在这个项目中，我们将开发和测试一种新的近红外成像平台的可行性， 石墨烯量子点（GQD）满足近红外生物成像的关键需求： NIR（950 nm以上），具有NIR激发，高生物相容性，光稳定性和能力 用于活体动物模型中的药物追踪和体内近红外成像。这将分3个步骤实施： (1)通过自下而上和自上而下的方法合成NIR发射GQD，并表征 它们的光学和物理性质，（2）测试GQD用于NIR体外成像并评估它们的光学和物理性质。 生物相容性以及（3）在活体动物中进行GQD NIR荧光的体内成像 作为离体器官组织成像，定量切除器官中的GQD含量。我们将伴随着 评估潜在的不良反应，以选择无毒的GQD候选物。在这个过程中，各种 的合成GQD结构将经历严格的3步选择的能力（1）高 产生NIR荧光，（2）细胞中的高生物相容性和NIR成像，（3）活体内的NIR成像 具有最小/无毒性的镇静动物。所选择的GQD候选物将使体内动物 使用非侵入性实时图像跟踪测试治疗输送， 牺牲的动物从长远来看，我们预计这些GQD平台将成为 在患者体内进行无创近红外传感。因此，拟议的倡议将解决几个问题， 生物技术的重要领域及其发展将最终有助于 改善人类健康。

项目成果

Detection of Pancreatic Cancer miRNA with Biocompatible Nitrogen-Doped Graphene Quantum Dots.

• DOI: 10.3390/ma15165760
• 发表时间: 2022-08-20
• 期刊: Materials (Basel, Switzerland)

Automated Approach to In Vitro Image-Guided Photothermal Therapy with Top-Down and Bottom-Up-Synthesized Graphene Quantum Dots.

• DOI: 10.3390/nano13050805
• 发表时间: 2023-02-22
• 期刊: Nanomaterials (Basel, Switzerland)
• 作者: Lee B;Stokes GA;Valimukhametova A;Nguyen S;Gonzalez-Rodriguez R;Bhaloo A;Coffer J;Naumov AV
• 通讯作者: Naumov AV

Doped Graphene Quantum Dots as Biocompatible Radical Scavenging Agents.

• DOI: 10.3390/antiox12081536
• 发表时间: 2023-07-31
• 期刊: Antioxidants (Basel, Switzerland)

Cancer Therapeutic siRNA Delivery and Imaging by Nitrogen- and Neodymium-Doped Graphene Quantum Dots.

• DOI: 10.1021/acsbiomaterials.3c00369
• 发表时间: 2023-05
• 期刊: ACS biomaterials science & engineering
• 影响因子: 5.8
• 作者: Alina Valimukhametova;B. Lee;U. C. Topkiran;Klara Gries;R. Gonzalez-Rodriguez;J. Coffer;G. Akkaraju;A. Naumov