Orally Delivered Co@NCNH/NC Nanoparticles and an Adhesive Magnetic Microneedle Patch for Magnetically Amplified Bioelectronic Therapy of Colorectal Cancer

ABSTRACT Effective management of colorectal cancer remains hindered by inadequate local drug retention, poor intratumoral penetration, and profound immunosuppression. Here, we developed a magnetically amplified bioelectronic platform integrating orally ingestible Co@NCNH/NC nanoparticles with an adhesive magnetic microneedle patch, operating under a rotating magnetic field (RMF). Co@NCNH/NC nanoparticles are cobalt‐infused nitrogen‐doped carbon hybrids with magnetic responsiveness and robust interfacial electroactivity. The microneedle patch features a polydopamine‐modified gelatin methacryloyl adhesive base for stable wet‐tissue fixation onto the colonic wall and magnetized tips that facilitate local magnetic enrichment of Co@NCNH/NC nanoparticles. After oral administration, Co@NCNH/NC nanoparticles transit to the colorectal region, where the microneedle patch captures and concentrates them at the tumor site, enhancing local retention and penetration. Under RMF stimulation, the microneedle tips and retained Co@NCNH/NC nanoparticles cooperatively generate intensified local electrical and electrochemical outputs, triggering mitochondrial depolarization, DNA damage, calcium overload, and concurrent apoptosis and pyroptosis. Critically, this bioelectrical insult provokes robust immunogenic responses—including calreticulin exposure and High Mobility Group Box 1 release—that promote dendritic cell maturation, macrophage M1 repolarization, elevated NK cell infiltration, and augmented CD4 + and CD8 + T‐cell activity. In orthotopic colorectal tumor‐bearing mice, this combination treatment markedly suppresses primary tumor growth and intra‐abdominal metastasis, prolongs survival, and remodels tumor‐associated gut microbial dysbiosis.