Iron-based magnetic nanoplatforms for immune microenvironment remodeling and cancer immunotherapy: progress and...

Cancer continues to be one of the leading causes of death worldwide. Although immunotherapy has transformed oncologic treatment by mobilizing the host immune system, the immunosuppressive tumor immune microenvironment (TIME) still constitutes a major barrier to durable clinical responses. Recent studies indicate that iron-based magnetic nanoparticles (Fe-MNPs) offer capabilities that extend beyond those of conventional drug delivery systems, acting instead as active regulators of the TIME. In this review, we outline current progress in Fe-MNP-mediated cancer immunotherapy and propose a conceptual framework to clarify their immunomodulatory effects. Specifically, Fe-MNPs can generate multiple physicochemical stimuli under magnetic field control, including magnetic hyperthermia, magnetically induced mechanical perturbation, and Fenton reaction-mediated oxidative stress. These upstream events converge to induce immunogenic stress, including ferroptosis-associated injury, which in turn promotes hypoxia alleviation, tumor-associated macrophage (TAM) reprogramming, dendritic cell activation, and enhanced effector T-cell responses. Together, these findings support a framework in which Fe-MNP-mediated immunomodulation is understood as an integrated cascade rather than a collection of isolated effects. However, challenges remain regarding biosafety, long-term iron metabolism, delivery efficiency, and large-scale manufacturing. Overall, this review provides a systematic overview of Fe-MNP-mediated immunomodulation and discusses the translational prospects of these materials as multifunctional platforms for cancer immunotherapy.