State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Amy Medical University), Chongqing 400038, China.
Theranostics. 2020 Aug 8;10(22):10106-10119. doi: 10.7150/thno.48448. eCollection 2020.
Ulcerative colitis (UC) is featured with relapsing inflammation in the colon, where macrophages are recruited and polarized locally into M1 type to drive further inflammation. Pharmacotherapy of UC has exhibited limited efficacy, mostly due to the poor specificity. A macrophage-biomimetic nanomedicine was developed for targeted treatment of UC, which was derived from reactive oxygen species (ROS)-sensitive β-cyclodextrin, loaded with rosiglitazone, and coated with macrophage membrane. The ability of the nanomedicine in regulating macrophage polarization was examined at cellular level, and the macrophage-tropism driven targeted delivery into the inflammatory colon was investigated by bio-imaging distribution assay. Furthermore, the nanomedicine's therapeutic efficacy was systemically examined in dextran sulfate sodium (DSS)-induced colitis model in mice. The nanomedicine effectively polarized macrophages to M2 and protected epithelial cells from oxidative stress . In addition, macrophage-membrane led the nanomedicine to the inflammatory colon with a high targeting efficiency. In response to the elevated ROS in the inflammatory tissue, the nanomedicine released rosiglitazone specifically and regulated macrophage polarization . Macrophage membrane also assisted inflammation suppression by sequestering proinflammatory cytokines. Working in such a synergy, the nanomedicine exhibited significant therapeutic effects against UC in mice. This macrophage-biomimetic nanomedicine leverages the inflammatory tropism and inflammatory cytokine sequestration effects of macrophage membrane for targeted delivery and local inflammation suppression, the ROS-responsiveness of β-cyclodextrin-based matrix for specific payload release, and the macrophage-polarizing effect of rosiglitazone for inflammatory regulation, thereby exhibiting considerable therapeutic efficacy against UC in mice. This study offers important new insights on the design and development of biomimetic nanomaterials for inflammation regulations.
溃疡性结肠炎（UC）的特征是结肠反复发作炎症，巨噬细胞被招募并在局部极化为 M1 型以进一步引发炎症。UC 的药物治疗疗效有限，主要是因为缺乏特异性。本研究开发了一种巨噬细胞仿生纳米医学，用于靶向治疗 UC，它源自对活性氧（ROS）敏感的β-环糊精，负载罗格列酮，并涂有巨噬细胞膜。在细胞水平上研究了纳米医学调节巨噬细胞极化的能力，并通过生物成像分布分析研究了由巨噬细胞趋向性驱动的靶向递送至炎症结肠的情况。此外，还在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中系统地检查了纳米医学的治疗效果。该纳米医学有效地将巨噬细胞极化为 M2 型，并保护上皮细胞免受氧化应激。此外，巨噬细胞膜使纳米医学能够以高靶向效率递送至炎症结肠。针对炎症组织中升高的 ROS，纳米医学特异性释放罗格列酮并调节巨噬细胞极化。巨噬细胞膜还通过隔离促炎细胞因子协助抑制炎症。这种协同作用使纳米医学在小鼠中对 UC 表现出显著的治疗效果。这种巨噬细胞仿生纳米医学利用了巨噬细胞膜的炎症趋向性和炎症细胞因子隔离作用，用于靶向递药和局部炎症抑制，基于β-环糊精的基质的 ROS 响应性用于特异性有效载荷释放，以及罗格列酮的巨噬细胞极化作用用于炎症调节，从而在小鼠中对 UC 表现出相当大的治疗效果。本研究为炎症调节的仿生纳米材料的设计和开发提供了重要的新见解。
