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.

项目摘要/摘要 该项目的主要目标是开发一种新型的计算机断层扫描(CT)造影剂，即， 葡聚糖包被氧化铈纳米颗粒(Dex-CENP)对患者胃肠道(GIT)的成像 患有炎症性肠病(IBD)，也可用于治疗和改善人们的生活质量 患有IBD。目前临床上使用碘和钡为基础的造影剂用于胃肠道CT成像。 然而，这些造影剂不是针对炎症部位的，限制了它们对IBD的诊断作用 成像。因此，迫切需要开发用于这一应用的新型CT造影剂。Ce是一种 由于其强大的CT对比度产生能力，有可能用作新型造影剂。尽管如此，Ce 用于CT成像的造影剂很少被研究。除了极佳的x射线对比度外，Ce3+ 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(如类固醇)， 抗生素，以及生物靶向促炎肿瘤坏死因子途径。然而，这些 治疗并不是对所有患者都有效，而且有很大的局限性，因为这些治疗的效果是 不会很久的。一些研究强调了氧化应激在IBD中的作用。石油产量的增加 活性氧物种(ROS)与总抗氧化能力的降低相结合，导致相当大的 炎症性肠病慢性炎症结肠粘膜的氧化应激。最近的研究表明，抗氧化剂 用药对IBD的治疗可能是有益的。氧化铈纳米颗粒已被提议作为一种 人工抗氧化剂，因为它们中和自由基，因此他们可能会减轻IBD患者的症状。 葡聚糖涂层将被用来提供纳米颗粒的稳定性，同时保持催化活性并鼓励 瞄准发炎部位。这项提议将检验地塞米松-CENP将在IBD积聚的假设 炎症部位，允许用CT检测，它们可以有益于IBD患者，因为 它们的抗氧化性。 拟议的研究将为申请者提供一个获得以下领域技能的机会 纳米粒子合成、CT成像及IBD治疗。将为该项目提供培训和支持 由一个多学科的指导团队。这项工作的开展将推动诊断和治疗方案的发展 并提供丰富的培训经验，为申请者未来的成功做好准备。