Dual-responsive biohybrid neutrobots for active target delivery

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 hardto-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.

Automated summary

Neutrophil-based microrobots, constructed by phagocytosis of drug-loaded magnetic nanogels enveloped in Escherichia coli membrane, exhibit controllable intravascular movement and can autonomously aggregate in the brain by positive chemotactic motion along the gradient of inflammatory factors. These dual-responsive neutrobots show promise for targeted drug delivery to inhibit tumor cell proliferation compared to traditional drug injection, leveraging the biological characteristics of natural neutrophils that artificial microrobots cannot replicate.