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.

Synthetic micro/nanomotors have attracted considerable attention due to their promising potential in the field of biomedicine.

Gallium-based liquid metals have been extensively studied in the field of biomedical engineering, including applications in tumor and inflammatory disease therapy, as well as targeted drug delivery. Among these, leveraging the photothermal effect of gallium liquid metals enables effective treatment of heat-sensitive cells in tumor regions and enhances the diffusion capability of liquid metal microdroplets. However, research on the active treatment of ulcerative colitis (UC) using photothermal therapy with liquid metals remains unexplored. This study focuses on constructing an active composite colloidal motor based on gallium indium liquid metal alloy, using liquid metal microdroplets as the core. Through layer-by-layer assembly of polyelectrolytes, a liquid metal active droplet loaded with the drug mesalazine (5-aminosalicylic acid), named as LMAD-A was developed. Under asymmetric light fields generated by NIR-II light source irradiation, LMAD-A exhibits autonomous locomotion, achieving an effective diffusion coefficient more than 800 times greater than that of Brownian motion in liquid metal microdroplets of similar size. Furthermore, LMAD-A demonstrates phototactic behavior, moving toward the NIR light source autonomously. Through in vitro and in vivo experiments in mice, it was verified that LMAD-A can aggregate, deform, and fuse in the mouse colon under photothermal effects, leading to enhanced release of the loaded drug. In simulated treatments, LMAD-A significantly alleviated DSS-induced colitis in mice, confirming the targeted therapeutic capability of active liquid metal microdroplets as an active therapeutic agent in UC-affected regions.

Magnetic nanoparticles, with their excellent biocompatibility and biodegradability, serve as ideal materials for constructing targeted drug delivery systems. Iron oxide (Fe₃O₄) nanoparticles, controllably prepared via methods such as solvothermal synthesis, can be combined with mesoporous silica to construct magnetically steerable nanorobots. Such robots enable efficient drug loading and precise delivery. To address challenges in the treatment of Inflammatory Bowel Disease (IBD), including the significant side effects of systemic drugs and the low oral bioavailability and poor colonic targeting of novel food-derived drugs (e.g., capsaicin with anti-inflammatory activity), this study designed capsaicin-loaded iron oxide-mesoporous silica composite nanorobots (Cap-M@mSbots). Driven by a rotating gradient magnetic field of up to 80 mT, Cap-M@mSbots achieve large-scale emergent collective locomotion, with a maximum collective locomotion velocity reaching 180.7 μm/s, and are capable of long-distance movement overcoming millimeter-scale obstacles. This system can be actively propelled to colonic lesion sites under magnetic guidance, achieving targeted drug enrichment and sustained release, thereby offering a novel strategy for the targeted therapy of IBD.

An urgent requirement in chimeric antigen receptor (CAR) immune cell therapy [e.g., CAR–natural killer (NK) cells] for solid tumors is to engineer the cells for precise tumor targeting. Meanwhile, medical microrobots can be navigated toward specific target sites using external magnetic fields. Here, by bridging these approaches, we turn CAR-NK cells into magnetic biohybrid microrobots (CAR-NK microrobots) that achieve controllable long-distance targeted navigation at therapeutic doses (∼10 ⁶ cells) in both murine and nonhuman primate animal models in vivo. CAR-NK microrobots are developed through genetic engineering with CAR structures and loading with magnetic nanoparticles for field-based navigation. Different magnetic field inputs reconfigure their swarms between vortex and ribbon modes, allowing dense aggregation for targeted navigation and further broad dispersion for large-area coverage. Using programmable magnetic fields, in vivo CAR-NK microrobot–based therapy is demonstrated for metastatic leptomeningeal carcinomatosis in brain’s cerebrospinal fluid space. After intrathecal injection, the microrobots are magnetically guided long distance through the spinal canal toward the brain in vortex mode and subsequently spread over the target site in ribbon mode, as visualized by real-time angiographic imaging in a nonhuman primate model, providing a proof-of-feasibility demonstration in a nonhuman primate anatomical setting.