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bioRxiv · 10.64898/2026.05.29.728625

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

Zeng, X.·Zhang, Y.·Wu, C.·Fan, M.·Duan, Q.·Cai, S.·Yasa, I. C.
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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.

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Zeng, X., Zhang, Y., Wu, C., Fan, M., Duan, Q., Cai, S., Yasa, I. C.. 2026-06-02. Magnetically guided macrophage immunobots coordinate iron-metabolic cascades and immunogenic ferroptosis for tumor immunotherapy. https://doi.org/10.64898/2026.05.29.728625

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