Rosario-Berríos Derick N, Pang Amanda Y, Mossburg Katherine J, Kim Johoon, Vázquez Marrero Víctor R, Yoon Seokyoung, Gupta Mahima, Lenz Olivia C, Liu Leening P, Kian Andrea C, La Luz Rivera Kálery, Shin Sunny, Noël Peter B, Lennon Elizabeth M, Cormode David P
Department of Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Radiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Nanoscale. 2025 Apr 17;17(16):10356-10370. doi: 10.1039/d4nr04994b.
Inflammatory bowel disease (IBD) affects approximately 3.1 million individuals in the U.S., causing deleterious symptoms such as bloody diarrhea and leading to an increased risk of colorectal cancer. Effective imaging is crucial for diagnosing and managing IBD, as it allows for accurate assessment of disease severity, guides treatment decisions, and monitors therapeutic responses. Computed tomography (CT) with contrast agents is the gold standard for imaging the gastrointestinal tract (GIT). However, current agents are less effective in obese patients and lack specificity for inflamed regions associated with IBD. Moreover, IBD treatments often have limited efficacy and do not address the role of oxidative stress in IBD progression. This study explores dextran-coated cerium oxide nanoparticles (Dex-CeNP) as a CT contrast agent and therapeutic for IBD, leveraging cerium's superior K-edge energy profile, dextran's inflammation-specific targeting, and cerium oxide's antioxidant properties. Herein, we synthesized Dex-CeNP formulations using 5, 10, 25, and 40 kDa dextran to explore the effect of dextran coating molecular weight. assays showed formulation biocompatibility and demonstrated that 5 kDa Dex-CeNP had the highest catalytic activity, which translated into improved suppression of inflammation. As a result, this formulation was selected for use. CT imaging of mice subjected to dextran sodium sulfate (DSS) colitis showed that Dex-CeNP provided better contrast in the GIT of mice with colitis compared to iopamidol (ISO), with pronounced attenuation in the large intestine and disease- specific retention at 24 h. Additionally, Dex-CeNP significantly decreased Disease Activity Index (DAI) scores, and diminished gastrointestinal bleeding when compared with a currently approved drug, indicating that it is an effective treatment for colitis. Studies also revealed that the Dex-CeNPs were safe and well-excreted following administration. In summary, Dex-CeNP has significant promise as a dual-purpose agent for CT imaging and treatment of IBD.
炎症性肠病(IBD)在美国影响着约310万人,会引发诸如便血腹泻等有害症状,并导致结直肠癌风险增加。有效的成像对于IBD的诊断和管理至关重要,因为它能够准确评估疾病严重程度、指导治疗决策并监测治疗反应。使用造影剂的计算机断层扫描(CT)是胃肠道(GIT)成像的金标准。然而,目前的造影剂在肥胖患者中效果较差,且对与IBD相关的炎症区域缺乏特异性。此外,IBD治疗通常疗效有限,且未涉及氧化应激在IBD进展中的作用。本研究探索了葡聚糖包被的氧化铈纳米颗粒(Dex-CeNP)作为一种用于IBD的CT造影剂和治疗剂,利用铈优越的K边能量谱、葡聚糖对炎症的特异性靶向作用以及氧化铈的抗氧化特性。在此,我们使用5、10、25和40 kDa的葡聚糖合成了Dex-CeNP制剂,以探究葡聚糖包被分子量的影响。检测显示了制剂的生物相容性,并证明5 kDa的Dex-CeNP具有最高的催化活性,这转化为对炎症的更好抑制。因此,选择该制剂用于后续研究。对接受葡聚糖硫酸钠(DSS)诱导结肠炎的小鼠进行CT成像显示,与碘帕醇(ISO)相比,Dex-CeNP在结肠炎小鼠的胃肠道中提供了更好的对比度,在大肠中有明显的衰减,且在24小时时有疾病特异性滞留。此外,与一种目前已获批的药物相比,Dex-CeNP显著降低了疾病活动指数(DAI)评分,并减少了胃肠道出血,表明它是一种有效的结肠炎治疗药物。研究还表明,Dex-CeNPs给药后安全且排泄良好。总之,Dex-CeNP作为一种用于IBD的CT成像和治疗的两用药物具有巨大潜力。