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

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.

Hydrogen‐Powered Microswimmers for Precise and Active Hydrogen Therapy Towards Acute Ischemic Stroke

Biodegradable microswimmers offer great potential for minimally invasive targeted therapy due to their tiny scale, multifunctionality, and versatility. However, most of the reported systems focused on the proof‐of‐concept on the in vitro level. Here, the successful fabrication of facile hydrogen‐powered microswimmers (HPMs) for precise and active therapy of acute ischemic stroke is demonstrated. The hydrogen (H2) generated locally from the designed magnesium (Mg) microswimmer functions not only as a propellant for motion, but also as an active ingredient for reactive oxygen species (ROS) and inflammation scavenging. Due to the continuous detachment of the produced H2, the motion of the microswimmers results in active H2 delivery that allows for enhanced extracellular and intracellular reducibility. With the help of a stereotaxic apparatus device, HPMs were injected precisely into the lateral ventricle of middle cerebral artery occlusion (MCAO) rats. By scavenging ROS and inflammation via active H2, MCAO rats exhibit significant decrease in infarct volume, improved spatial learning and memory capability with minimal adverse effects, demonstrating efficient efficacy on anti‐ischemic stroke. The as‐developed HPMs with excellent biocompatibility and ROS scavenging capability holds great promise for the treatment of acute ischemic stroke or other oxidative stress induced diseases in clinic in the near future.