Zhang Mingzhen, Viennois Emilie, Prasad Meena, Zhang Yunchen, Wang Lixin, Zhang Zhan, Han Moon Kwon, Xiao Bo, Xu Changlong, Srinivasan Shanthi, Merlin Didier
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Biomaterials. 2016 Sep;101:321-40. doi: 10.1016/j.biomaterials.2016.06.018. Epub 2016 Jun 9.
There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ∼230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ∼125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
对于慢性衰弱性炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎,临床上需要新的、更有效的治疗方法。在本研究中,我们对源自可食用生姜的特定纳米颗粒群体(GDNPs 2)进行了表征,并证明了它们口服给药后能有效靶向结肠。GDNPs 2的平均尺寸约为230纳米,呈现负zeta电位。这些纳米颗粒含有高水平的脂质、一些蛋白质、约125种微小RNA(miRNA)以及大量生姜生物活性成分(6-姜酚和6-姜烯酚)。我们还证明GDNPs 2主要被肠上皮细胞(IEC)和巨噬细胞摄取,且无毒。使用不同的小鼠结肠炎模型,我们表明GDNPs 2减轻了急性结肠炎,增强了肠道修复,并预防了慢性结肠炎和结肠炎相关癌症(CAC)。二维差异凝胶电泳/质谱分析进一步确定了参与这些小鼠模型的GDNPs 2的分子靶点候选物。在结肠炎模型中,口服GDNPs 2提高了IEC的存活率和增殖率,降低了促炎细胞因子(TNF-α、IL-6和IL-1β),并增加了抗炎细胞因子(IL-10和IL-22),这表明GDNPs 2有潜力在促进愈合作用的同时减弱损伤因素。总之,源自可食用生姜的纳米颗粒GDNPs 2代表了一种新型的天然递送机制,可改善IBD的预防和治疗,还有额外的好处,即克服了诸如潜在毒性和合成纳米颗粒常见的生产规模有限等局限性。