Liu Jun, Wang Yixin, Heelan William John, Chen Yu, Li Zhaoting, Hu Quanyin
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.
Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Sci Adv. 2022 Nov 11;8(45):eabp8798. doi: 10.1126/sciadv.abp8798.
Inflammatory bowel diseases (IBDs) are often associated with elevated levels of reactive oxygen species (ROS) and highly dysregulated gut microbiota. In this study, we synthesized a polymer of hyaluronic acid-poly(propylene sulfide) (HA-PPS) and developed ROS-scavenging nanoparticles (HPN) that could effectively scavenge ROS. To achieve colon tissue targeting effects, the HPN nanoparticles were conjugated to the surface of modified probiotic Nissle 1917 (EcN). To enhance the bacteriotherapy of EcN, we encapsulated EcN cells with a poly-norepinephrine (NE) layer that can protect EcN against environmental assaults to improve the viability of EcN in oral delivery and prolong the retention time of EcN in the intestine due to its strong mucoadhesive capability. In the dextran sulfate sodium-induced mouse colitis models, HPN-NE-EcN showed substantially enhanced prophylactic and therapeutic efficacy. Furthermore, the abundance and diversity of gut microbiota were increased after treatment with HPN-NE-EcN, contributing to the alleviation of IBDs.
炎症性肠病（IBDs）通常与活性氧（ROS）水平升高和肠道微生物群高度失调有关。在本研究中，我们合成了透明质酸-聚硫化丙烯（HA-PPS）聚合物，并开发了能够有效清除ROS的纳米颗粒（HPN）。为了实现结肠组织靶向作用，将HPN纳米颗粒偶联到经修饰的益生菌Nissle 1917（EcN）表面。为了增强EcN的细菌疗法，我们用聚去甲肾上腺素（NE）层包裹EcN细胞，该层可以保护EcN免受环境攻击，从而提高EcN口服给药的存活率，并因其强大的粘膜粘附能力延长EcN在肠道中的保留时间。在葡聚糖硫酸钠诱导的小鼠结肠炎模型中，HPN-NE-EcN显示出显著增强的预防和治疗效果。此外，用HPN-NE-EcN治疗后，肠道微生物群的丰度和多样性增加，有助于缓解IBDs。
