Micromotor-Enabled Active Hydrogen and Tobramycin Delivery for Synergistic Sepsis Therapy

微电机驱动活性氢和妥布霉素输送用于协同脓毒症治疗

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作者:Yanzhen Song, Ruotian Zhang, Hanfeng Qin, Wenxin Xu, Jia Sun, Jiamiao Jiang, Yicheng Ye, Junbin Gao, Huaan Li, Weichang Huang, Kun Liu, Yunrui Hu, Fei Peng, Yingfeng Tu

Abstract

Sepsis is a highly heterogeneous syndrome normally characterized by bacterial infection and dysregulated systemic inflammatory response that leads to multiple organ failure and death. Single anti-inflammation or anti-infection treatment exhibits limited survival benefit for severe cases. Here a biodegradable tobramycin-loaded magnesium micromotor (Mg-Tob motor) is successfully developed as a potential hydrogen generator and active antibiotic deliverer for synergistic therapy of sepsis. The peritoneal fluid of septic mouse provides an applicable space for Mg-water reaction. Hydrogen generated sustainably and controllably from the motor interface propels the motion to achieve active drug delivery along with attenuating hyperinflammation. The developed Mg-Tob motor demonstrates efficient protection from anti-inflammatory and antibacterial activity both in vitro and in vivo. Importantly, it prevents multiple organ failure and significantly improves the survival rate up to 87.5% in a high-grade sepsis model with no survival, whereas only about half of mice survive with the individual therapies. This micromotor displays the superior therapeutic effect of synergistic hydrogen-chemical therapy against sepsis, thus holding great promise to be an innovative and translational drug delivery system to treat sepsis or other inflammation-related diseases in the near future.

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