Inspired by the highly versatile natural motors, artificial micro‐/nanomotors that can convert surrounding energies into mechanical motion and accomplish multiple tasks are devised. In the past few years, micro‐/nanomotors have demonstrated significant potential in biomedicine. However, the practical biomedical applications of these small‐scale devices are still at an infant stage. For successful bench‐to‐bed translation, biocompatibility of micro‐/nanomotor systems is the central issue to be considered. Herein, the recent progress in micro‐/nanomotors in biocompatibility is reviewed, with a special focus on their biomedical applications. Through close collaboration between researches in the nanoengineering, material chemistry, and biomedical fields, it is expected that a promising real‐world application platform based on micro‐/nanomotors will emerge in the near future.

Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2 into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2 nanoparticles with catalytic activity for active Fenton-like Mn2+ delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+ is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.

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.

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