Swimming biohybrid microsized robots (e.g., bacteria- or sperm-driven microrobots) with self-propelling and navigating capabilities have become an exciting field of research, thanks to their controllable locomotion in hard-to-reach areas of the body for noninvasive drug delivery and treatment. However, current cell-based microrobots are susceptible to immune attack and clearance upon entering the body. Here, we report a neutrophil-based microrobot (“neutrobot”) that can actively deliver cargo to malignant glioma in vivo. The neutrobots are constructed through the phagocytosis of Escherichia coli membrane-enveloped, drug-loaded magnetic nanogels by natural neutrophils, where the E. coli membrane camouflaging enhances the efficiency of phagocytosis and also prevents drug leakage inside the neutrophils. With controllable intravascular movement upon exposure to a rotating magnetic field, the neutrobots could autonomously aggregate in the brain and subsequently cross the blood-brain barrier through the positive chemotactic motion of neutrobots along the gradient of inflammatory factors. The use of such dual-responsive neutrobots for targeted drug delivery substantially inhibits the proliferation of tumor cells compared with traditional drug injection. Inheriting the biological characteristics and functions of natural neutrophils that current artificial microrobots cannot match, the neutrobots developed in this study provide a promising pathway to precision biomedicine in the future.
Swimming microrobots guided in the circulation system offer considerable promise in precision medicine but currently suffer from problems such as limited adhesion to blood vessels, intensive blood flow, and immune system clearance—all reducing the targeted interaction. A swimming microrobot design with clawed geometry, a red blood cell (RBC) membrane–camouflaged surface, and magnetically actuated retention is discussed, allowing better navigation and inspired by the tardigrade’s mechanical claw engagement, coupled to an RBC membrane coating, to minimize blood flow impact. Using clinical intravascular optical coherence tomography in vivo, the microrobots’ activity and dynamics in a rabbit jugular vein was monitored, illustrating very effective magnetic propulsion, even against a flow of ~2.1 cm/s, comparable with rabbit blood flow characteristics. The equivalent friction coefficient with magnetically actuated retention is elevated ~24-fold, compared to magnetic microspheres, achieving active retention at 3.2 cm/s, for >36 hours, showing considerable promise across biomedical applications.