Macrophage-Biomimetic Nanoparticles Ameliorate Ulcerative Colitis through Reducing Inflammatory Factors Expression

作者：Zhengshuo Li, Xiaoyue Zhang, Can Liu, Peng Qiu, Yangge Wu, Yuqing Wen, Run Zheng, Qun Yan, Jian Ma · 发表于：Journal of Innate Immunity · 年份：2021 · DOI：10.1159/000519363 · 被引用次数：50 · 研究领域：Inflammatory Bowel Disease、S100 Proteins and Annexins、Immune cells in cancer

BACKGROUND AND AIMS: Inflammatory mediator S100A9 is dramatically elevated in ulcerative colitis and correlates with disease severity. S100A9 is a potential molecule to target for the treatment of colitis, but to date, there is no effective targeting method. The aim of this study was to develop a safe and effective nano-delivery system targeting S100A9 and to evaluate its therapeutic efficacy in ulcerative colitis mouse model. METHODS: We designed an oral nano-delivery system using poly (lactic acid-glycolic acid) (PLGA)-loaded S100A9 inhibitor tasquinimod to synthesize PLGA-TAS nanoparticles. TLR4-overexpressing macrophage membranes (MMs) were used to wrap the nanoparticles to make MM-PLGA-TAS, which allowed the nanoparticles to acquire the ability to specifically enrich the colitis region. RESULTS: MM-PLGA-TAS was endocytosed by inflammatory phenotype RAW264.7 cells in vitro and can efficiently enrich in inflamed mouse colitis tissue in vivo. A chemically induced ulcerative colitis mouse model was used to evaluate the therapeutic effect of oral MM-PLGA-TAS. MM-PLGA-TAS significantly alleviated the symptoms of ulcerative colitis, and mechanically, MM-PLGA-TAS achieved immunomodulatory and suppressive effects by reducing S100a9 and other cytokines in the colitis region. CONCLUSION: We describe a convenient, orally targeted colitis drug delivery system that cures the disease in ulcerative colitis mice. This system substantially increases drug accumulation in inflamed colonic t...