SPION-functionalized CAR-T cells: Overcoming key barriers in solid tumor therapy

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies, but its efficacy in solid tumors remains limited. Major barriers include heterogenous antigen expression, poor tumor infiltration, and a strongly immunosuppressive tumor microenvironment. In addition, systemic administration of potent CAR-T cells frequently causes severe toxicities such as cytokine release syndrome (CRS) and neurotoxicity. Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as multifunctional tools to address these challenges. They enable magnetic field-guided accumulation of CAR-T cells at tumor sites, potentially overcoming infiltration barriers and reducing systemic exposure. Simultaneously, their magnetic properties allow non-invasive tracking by magnetic resonance imaging (MRI). This review summarizes recent advances in SPION-functionalized CAR-T cells, highlighting their potential to enhance solid tumor therapy by improving targeting, reducing systemic toxicity, and enabling real-time imaging.