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Abstract：
BACKGROUND: Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging.
METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice.
RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission.
CONCLUSIONS: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.
METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice.
RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission.
CONCLUSIONS: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.
摘要：
背景：炎症性肠病（IBD）是胃肠道（GIT）的进行性和衰弱性炎症性疾病。尽管最近取得了进展，精确的治疗和无创监测仍然具有挑战性。
方法：这里，我们开发了口服，结肠炎靶向和透明质酸（HA）修饰，核壳姜黄素（Cur）和氧化铈（CeO2）纳米探针（Cur@PC-HA/CeO2NPs）用于计算机断层扫描（CT）成像指导治疗和监测活体小鼠IBD。
结果：口服后，高分子量HA保持完整性，在上部GIT中几乎没有吸收，然后由于其结肠炎靶向能力而活跃地积聚在局部结肠炎部位，导致持续24小时的特定CT增强。保留的NPs被结肠中的透明质酸酶进一步降解以释放Cur和CeO2，从而发挥抗炎和抗氧化作用。结合NPs调节肠道菌群的能力，口服NP导致症状的实质性缓解。经过多次治疗,高CT衰减的结肠逐渐减小的范围与临床生物标志物的变化相关,表明治疗反应和缓解的可行性。
结论：本研究为IBD合并治疗和实时监测治疗反应的新型治疗整合策略的设计提供了概念验证。
方法：这里，我们开发了口服，结肠炎靶向和透明质酸（HA）修饰，核壳姜黄素（Cur）和氧化铈（CeO2）纳米探针（Cur@PC-HA/CeO2NPs）用于计算机断层扫描（CT）成像指导治疗和监测活体小鼠IBD。
结果：口服后，高分子量HA保持完整性，在上部GIT中几乎没有吸收，然后由于其结肠炎靶向能力而活跃地积聚在局部结肠炎部位，导致持续24小时的特定CT增强。保留的NPs被结肠中的透明质酸酶进一步降解以释放Cur和CeO2，从而发挥抗炎和抗氧化作用。结合NPs调节肠道菌群的能力，口服NP导致症状的实质性缓解。经过多次治疗,高CT衰减的结肠逐渐减小的范围与临床生物标志物的变化相关,表明治疗反应和缓解的可行性。
结论：本研究为IBD合并治疗和实时监测治疗反应的新型治疗整合策略的设计提供了概念验证。
