Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Republic of Korea.
ACS Nano. 2023 Mar 14;17(5):4327-4345. doi: 10.1021/acsnano.2c08898. Epub 2023 Feb 6.
Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (HS) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned HS donor delivering liposome for spleen targeting (ST-HS lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-HS lipo and conventional long-circulating liposomes loaded with HS donors (LC-HS lipo) reduced the severity of colitis, whereas unloaded HS donors did not. Furthermore, the therapeutic effect of ST-HS lipo was superior to that of LC-HS lipo due to its better systemic immunomodulatory effect than that of LC-HS lipo. Our findings demonstrate that spleen targeting HS lipo may have therapeutic potential for IBD.
纳米颗粒在全身给药后主要被免疫细胞摄取。因此，它们被认为是免疫调节的理想药物递送载体。由于脾脏是最大的淋巴器官，调节全身免疫系统，因此已经有研究开发用于脾脏靶向的纳米颗粒来调节癌症和免疫性疾病的免疫。炎症性肠病（IBD）包括涉及胃肠道慢性炎症的疾病，尽管有多种治疗选择，但仍被认为是不可治愈的。硫化氢（HS）是执行抗炎功能的气体递质之一，在包括 IBD 在内的各种炎症性疾病中显示出有希望的免疫调节作用。在此，我们开发了一种经过精心调整的 HS 供体递送至脾脏的脂质体（ST-HS 脂质体），并在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中研究了其治疗效果。我们确定了理想的脂质体 PEG 类型和比例，以实现高稳定性、载药效率和脾脏靶向效果。在 DSS 诱导的结肠炎模型的治疗中，我们发现 ST-HS 脂质体和载有 HS 供体的常规长循环脂质体（LC-HS 脂质体）减轻了结肠炎的严重程度，而未载药的 HS 供体则没有。此外，由于 ST-HS 脂质体具有比 LC-HS 脂质体更好的全身免疫调节作用，因此其治疗效果优于 LC-HS 脂质体。我们的研究结果表明，脾脏靶向 HS 脂质体可能对 IBD 具有治疗潜力。
