CT imaging and therapy of inflammatory bowel disease via catalytic ceria nanoparticles

CT 成像和催化二氧化铈纳米粒子治疗炎症性肠病

• 批准号: 10755240
• 负责人: Derick Rosario
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10755240
• 关键词: Abdomen; Abdominal Cramps; Adult; Affect; Antibiotics; Antioxidants; Area; Barium; Barium Sulfate; Biodistribution; Biological; Biological Markers; Cell Survival; Cells; Cerium; Chronic; Clinic; Clinical; Clinical Chemistry; Coculture Techniques; Colon; Colonic inflammation; Colonoscopy; Contrast Media; Coupled; Custom; Data; Detection; Development; Dextrans; Diagnostic; Digestive System Disorders; Disease; Effectiveness; Elements; Endowment; Fatigue; Formulation; Free Radicals; Future; Gastrointestinal tract structure; Generations; Goals; Health Care Costs; Hemorrhagic colitis; Histology; Image; Imaging Techniques; Immunologic Stimulation; Immunosuppression; In Vitro; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Iodine; Link; Macrophage; Measurement; Measures; Medical Imaging; Mentors; Methodology; Molecular Weight; Mucous Membrane; New Agents; Overweight; Oxidative Stress; Pathway interactions; Patients; Performance; Persons; Plasma; Positioning Attribute; Predisposition; Production; Property; Quality of life; Reactive Oxygen Species; Research; Roentgen Rays; Role; Safety; Site; Steroids; Superoxide Dismutase; Suspensions; Symptoms; System; TNF gene; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Therapeutic immunosuppression; Tissues; Toxic effect; Training; Transmission Electron Microscopy; Treatment Protocols; United States; Vomiting; Work; X ray diffraction analysis; X ray spectroscopy; X-Ray Computed Tomography; aged; biological systems; biomaterial compatibility; catalase; cerium oxide nanoparticle; chronic inflammatory disease; colon cancer cell line; cytokine; dextran sulfate sodium induced colitis; diagnostic value; effective therapy; experience; experimental study; gastrointestinal imaging; imaging agent; imaging properties; improved; in vivo; indexing; light scattering; microCT; mimetics; multidisciplinary; murine colitis; nanoparticle; novel; novel therapeutics; obese patients; optical emission spectroscopy; oxidation; particle; reduce symptoms; side effect; skill acquisition; success; theranostics; therapeutically effective; treatment effect

PROJECT SUMMARY/ABSTRACT The principal goals of this project are to develop a novel computed tomography (CT) contrast agent, i.e., dextran coated cerium oxide nanoparticles (Dex-CeNP) to image the gastrointestinal tract (GIT) of those afflicted with inflammatory bowel disease (IBD) and that can also be used to treat and improve the quality of life of people with IBD. Iodine and barium-based contrast agents are currently used in the clinic for GIT imaging with CT. However, these contrast agents are not specific for inflammation sites, limiting their diagnostic utility for IBD imaging. Thus, there is a compelling need to develop novel CT contrast agents for this application. Cerium is a potential element to use for novel contrast agents due to its strong CT contrast generation. Despite this, cerium contrast agents have rarely been investigated for CT imaging. Aside from the excellent x-ray contrast, cerium possesses important properties for the treatment of IBD. Current management of IBD relies on nonspecific immunosuppressive therapies (such as steroids), antibiotics, and biologically targeting the pro-inflammatory tumor necrosis factor pathway. However, these treatments are not effective in all patients and have significant limitations, as the effects of these treatments are not long term. Several studies have highlighted the role of oxidative stress in IBD. The increased production of reactive oxygen species (ROS) in combination with reduced total antioxidant capacity results in considerable oxidative stress in the chronically inflamed colon mucosa of IBD. Recent studies have suggested that antioxidant administration may be beneficial in the treatment of IBD. Cerium oxide nanoparticles have been proposed as an artificial antioxidant as they neutralize free radicals, therefore they may reduce symptoms in patients with IBD. Dextran coating will be used to provide nanoparticle stability, while maintaining catalytic activity and encouraging targeting to sites of inflammation. This proposal will test the hypotheses that Dex-CeNP will accumulate in IBD inflammation sites to allow their detection with CT and that they can be beneficial to patients with IBD due to their antioxidant properties. The proposed research will provide an opportunity for the applicant to acquire skills in the areas of nanoparticle synthesis, CT imaging and treatment of IBD. Training and support for the project will be provided by a multi-disciplinary mentoring team. The pursuit of this work will advance the diagnostic and treatment options for IBD, as well as provide a rich training experience that will position the applicant for future success.

项目概要/摘要 该项目的主要目标是开发一种新型计算机断层扫描 (CT) 造影剂，即 右旋糖酐涂层氧化铈纳米颗粒 (Dex-CeNP) 用于对患者的胃肠道 (GIT) 进行成像 炎症性肠病（IBD），也可用于治疗和改善人们的生活质量 患有炎症性肠病。目前临床上使用碘和钡造影剂进行胃肠道 CT 成像。 然而，这些造影剂对炎症部位不具有特异性，限制了它们对 IBD 的诊断效用 成像。因此，迫切需要为此应用开发新型 CT 造影剂。铈是一种 由于其产生强大的 CT 造影剂，因此成为新型造影剂的潜在元素。尽管如此，铈 很少研究造影剂用于 CT 成像。除了出色的 X 射线对比度之外，铈 具有治疗 IBD 的重要特性。 目前 IBD 的治疗依赖于非特异性免疫抑制疗法（例如类固醇）， 抗生素，并从生物学上靶向促炎性肿瘤坏死因子途径。然而，这些 治疗并非对所有患者都有效，并且具有很大的局限性，因为这些治疗的效果是 不是长期的。多项研究强调了氧化应激在 IBD 中的作用。增加的产量 活性氧 (ROS) 与总抗氧化能力降低相结合会导致相当大的 IBD 慢性炎症结肠粘膜的氧化应激。最近的研究表明，抗氧化剂 施用可能有益于 IBD 的治疗。氧化铈纳米颗粒已被提议作为 人工抗氧化剂，因为它们可以中和自由基，因此可以减轻 IBD 患者的症状。 葡聚糖涂层将用于提供纳米颗粒稳定性，同时保持催化活性并鼓励 靶向炎症部位。该提案将测试 Dex-CeNP 将在 IBD 中积累的假设 炎症部位可通过 CT 进行检测，并且由于以下原因对 IBD 患者有益： 它们的抗氧化特性。 拟议的研究将为申请人提供获得以下领域技能的机会 纳米颗粒合成、CT 成像和 IBD 治疗。将为该项目提供培训和支持 由多学科的指导团队。这项工作的追求将推动诊断和治疗方案的发展 IBD，并提供丰富的培训经验，为申请人未来的成功做好准备。