CD5⁺ dendritic cell robots mediated in situ immunocyte activation

Immune cell microbots with self-propelling and navigating capabilities have become an exciting field of research. Isolation, activation, and adoptive transfer of cytotoxic immune cells in vitro are some of the most common technical methods. However, the ex situ activation and adoptive transfer of cytotoxic immune cells carry the risk of systemic inflammatory responses and functional exhaustion. To address this bottleneck, we report a CD5⁺ dendritic cell microbot (CD5⁺DC robot) constructed by engineering natural CD5⁺ dendritic cells to phagocytose magnetic nanoparticles coated with tumor cell membranes. The PD-L1 on the surface of CD5⁺ cells is preblocked to enhance immune activation capacity. Under switched exogenous rotating/conical magnetic fields, CD5⁺DC robots form chain-like clusters for upstream motion or ribbon-like clusters for downstream motion within the vasculature, enabling precise aggregation at intestinal targets. Then, they navigate along tumor chemokine gradients, penetrating the extracellular matrix barrier via positive chemotaxis to infiltrate deep into tumor tissues and trigger cascading activation of resident immune cells. Distinct from traditional cellular microbot therapies that rely on self-mediated cytotoxicity, this CD5⁺DC robot system activates durable antitumor immunity by reprogramming innate immune cells within the tumor microenvironment. This strategy offers a novel pathway toward precision-targeted therapy with excellent biocompatibility and functional stability.