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.

Magnesium-based micromotors for enhanced active and synergistic hydrogen chemotherapy

Hydrogen therapy has recently emerged as an attractive approach for combating major diseases including cancer, diabetes, stroke and Parkinson’s disease. Herein, we ingeniously fabricated a fully biodegradable Magnesium (Mg) based micromotor for the active hydrogen and chemotherapeutics delivery, and firstly proposed the concept of a self-propelled micromotor platform used for cancer active hydrogen-chemotherapy. By consuming water, the micromotor generates sufficient hydrogen in-situ, which is not only propellant for motion, but also active component for hydrogen therapy. The active motion of micromotors with a speed up to 57 ± 19 μm•s−1 leads to enhanced diffusion of produced hydrogen that allows for higher extracellular and intracellular reducibility. Compared with the non-motor control, the micromotor loaded with doxorubicin improves the chemotherapy efficacy significantly by 2.4 times for 4T1 tumor cells with a concentration as low as 100 μg•mL−1. These results indicate that the Mg-based micromotors can act as self-propelled carriers for enhanced intracellular hydrogen and cancer chemotherapy. Taking advantage of the locally hydrogen generation and the active moving capabilities, the facilely engineered Mg micromotor provides great promise for cancer synergistic hydrogen chemotherapy.