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.
26 October 2020 in Proceedings of the National Academy of Sciences
Significance: This work proposes reconfigurable multifunctional ferrofluid droplets as soft robots to overcome the limitation of existing magnetically actuated miniature soft robots based on elastomers, i.e., they cannot navigate inside very clustered and constrained spaces and reconfigure their shapes in situ for diverse tasks, due to limited deformability and predesigned shapes. We propose a fundamental mechanism of controlling reconfigurable large deformation (e.g., splitting) and coordinated motions of multiple ferrofluid droplets by programming external magnetic fields spatiotemporally. We employ this mechanism to achieve multiple functionalities, including on-demand liquid-cargo delivery, morphing for efficient and versatile manipulation of delicate objects, and programmable fluidic-mixing function, potentially enabling unprecedented functionalities in lab/organ-on-a-chip, fluidics, bioengineering, and medical device applications, beyond magnetically actuated elastomer-based soft robots.