Rosario-Berríos Derick N, Pang Amanda, Liu Leening P, Maidment Portia S N, Kim Johoon, Yoon Seokyoung, Nieves Lenitza M, Mossburg Katherine J, Adezio Andrew, Noël Peter B, Lennon Elizabeth M, Cormode David P
Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Department of Radiology, University of Pennsylvania, 3400 Spruce St, 1 SilversteinPhiladelphia, Pennsylvania 19104, United States.
Bioconjug Chem. 2025 Feb 19;36(2):233-244. doi: 10.1021/acs.bioconjchem.4c00507. Epub 2025 Jan 9.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. Contrast agents that provide enhanced imaging performance are highly valuable in this field. Recent studies have made significant progress in developing better contrast agents for imaging the gastrointestinal tract using nanoparticles. However, the impact of nanoparticle size on this application remains unexplored. Gold nanoparticles (AuNPs) serve as an ideal model to investigate the effect of nanoparticle size on imaging of the gastrointestinal tract due to their controllable synthesis across a broad size range. In this study, we synthesized AuNPs with core sizes ranging from 5 to 75 nm to examine the effect of the size in this setting. AuNPs were coated with poly(ethylene glycol) (PEG) to enhance stability and biocompatibility. In vitro tests show that gold nanoparticles are cytocompatible with macrophage cells (∼100% cell viability) and remain stable under acidic conditions, with no significant size changes over time. Phantom imaging studies using a clinical CT scanner indicated that there was no effect of nanoparticle size on CT contrast production, as previously demonstrated. imaging using a mouse model of acute colitis revealed a strong contrast generation throughout the GI tract for all agents tested. For the most part, contrast was independent of AuNP size, although AuNP outperformed iopamidol (a clinically approved control agent). In addition, differences in attenuation trends were observed between healthy and colitis mice. We also observed almost complete clearance at 24 h of all formulations tested (less than 0.7% ID/g was retained), supporting their value as a model platform for studying nanoparticle behavior in imaging. In conclusion, this study highlights the potential of nanoparticles as effective contrast agents for CT imaging of the gastrointestinal tract (GIT) in the UC. Further systemic research is needed to explore contrast agents that can specifically image disease processes in this disease setting.
溃疡性结肠炎（UC）是一种慢性炎症性肠病（IBD）。使用造影剂的CT成像常用于可视化UC患者的胃肠道（GI）。提供增强成像性能的造影剂在该领域具有很高的价值。最近的研究在开发使用纳米颗粒对胃肠道进行成像的更好造影剂方面取得了重大进展。然而，纳米颗粒大小对该应用的影响仍未得到探索。金纳米颗粒（AuNP）由于其在很宽的尺寸范围内可控制合成，是研究纳米颗粒大小对胃肠道成像影响的理想模型。在本研究中，我们合成了核心尺寸范围为5至75nm的AuNP，以研究该尺寸在这种情况下的影响。AuNP用聚乙二醇（PEG）包覆以增强稳定性和生物相容性。体外测试表明，金纳米颗粒与巨噬细胞具有细胞相容性（~100%细胞活力），并且在酸性条件下保持稳定，随时间没有明显的尺寸变化。使用临床CT扫描仪的体模成像研究表明，如先前所示，纳米颗粒大小对CT造影剂产生没有影响。使用急性结肠炎小鼠模型的成像显示，所有测试制剂在整个胃肠道中都产生了强烈的造影。在很大程度上，造影与AuNP大小无关，尽管AuNP的表现优于碘帕醇（一种临床批准的对照剂）。此外，在健康小鼠和结肠炎小鼠之间观察到了衰减趋势的差异。我们还观察到所有测试制剂在24小时时几乎完全清除（保留量小于0.7% ID/g），这支持了它们作为研究纳米颗粒在成像中行为的模型平台的价值。总之，本研究强调了纳米颗粒作为UC中胃肠道（GIT）CT成像有效造影剂的潜力。需要进一步的系统研究来探索能够在这种疾病环境中特异性成像疾病过程的造影剂。
