Magnetically guided macrophage immunobots coordinate iron-metabolic cascades and immunogenic ferroptosis for tumor immunotherapy

Abstract

Adoptive cell therapy (ACT) remains challenging in solid tumors, where poor tumor infiltration, metabolic heterogeneity, and an immunosuppressive tumor microenvironment (TME) constrain therapeutic efficacy. Here, we developed a magnetically actuated macrophage-based immune microrobot (immunobot) for active solid tumor immunotherapy. Immunobots were constructed by loading bone marrow-derived macrophages (BMDMs) with lipopolysaccharide-modified Janus L1-FePt magnetic microrollers (LMRs), enabling hard-magnetic actuation. Optimized LMR loading supported robust propulsion, retention under flow, and enhanced barrier penetration. LMRs further promoted M1-like polarization through LPS-driven inflammatory activation and FePt-derived labile iron-amplified oxidative stress, with altered iron homeostasis, increased reactive oxygen species (ROS), and enhanced NF-{kappa}B signaling. Immunobots also induced ferroptosis-associated immunogenic cell death in tumor cells. In vivo, magnetically guided immunobots suppressed tumor growth, reprogrammed tumor-associated macrophages (TAMs), promoted dendritic cell maturation, and enhanced CD8 T cell activation. This work establishes a microrobotic immunotherapy platform for active magnetic transport, iron-metabolic regulation, and immune remodeling in solid tumors.