环孢素 A 封装的 pH/ROS 双响应纳米制剂用于靶向治疗小鼠结肠炎,ACS Biomaterials Science & Engineering

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环孢素 A 封装的 pH/ROS 双响应纳米制剂用于靶向治疗小鼠结肠炎
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-09-21 , DOI: 10.1021/acsbiomaterials.3c01191
Shan Li _{1,

2} , Tianyu Wu ₁ , Jingfeng Wu ₁ , Jiangling Zhou ₃ , Hong Yang ₁ , Lei Chen ₁ , Wensheng Chen ₁ , Dinglin Zhang ₂

Affiliation

炎症性肠病（IBD）是一种多发病，严重影响患者的生活质量。为了减少不良反应并提高治疗效果，纳米药物已被广泛用于治疗IBD。然而，如何在炎症微环境下彻底释放有效负载并与IBD协同治疗还有待进一步研究。为了解决这个问题，使用 pH/ROS 响应材料作为载体，制备了负载环孢素 A (CsA)、叶酸 (FA) 修饰、pH 和活性氧 (ROS) 双响应的纳米颗粒 (FA-CsA NP) 。制备的 FA-CsA NPs 具有球形和均匀的尺寸分布，可以在酸和/或 ROS 微环境下巧妙地释放其有效负载。体外实验表明，FA-CsA NPs可以被活化的巨噬细胞有效内化，并且与游离药物或非靶向NPs相比，内化的NPs可以下调促炎细胞因子的表达。体内实验证实FA-CsA NPs在炎症结肠组织中显着积累，积累的NPs明显改善小鼠结肠炎症状，且无明显不良反应。总之，我们的结果为 IBD 的靶向治疗提供了候选方案。

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Cyclosporine A-Encapsulated pH/ROS Dual-Responsive Nanoformulations for the Targeted Treatment of Colitis in Mice

Inflammatory bowel disease (IBD) is a frequently occurring disease that seriously influences the patient’s quality of life. To decrease adverse effects and improve efficacy of therapeutics, nanomedicines have been widely used to treat IBD. However, how to thoroughly release payloads under an inflammatory microenvironment and synergistic therapy of IBD need to be further investigated. To address this issue, cyclosporine A (CsA)-loaded, folic acid (FA)-modified, pH and reactive oxygen species (ROS) dual-responsive nanoparticles (FA-CsA NPs) were fabricated using pH/ROS-responsive material as carrier. The prepared FA-CsA NPs had spherical shape and uniform size distribution and could smartly release their payloads under acid and/or ROS microenvironment. In vitro experiments demonstrated that FA-CsA NPs can be effectively internalized by activated macrophages, and the internalized NPs could down-regulate the expression of proinflammatory cytokines compared to free drug or nontargeted NPs. In vivo experiments verified that FA-CsA NPs significantly accumulated at inflammatory colon tissues and the accumulated NPs obviously improved the symptoms of colitis in mice without obvious adverse effects. In conclusion, our results provided a candidate for the targeted treatment of IBD.

更新日期：2023-09-21

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