Modulating the Blood–Brain Barrier via Magnetic Nano Systems–Mediated Hyperthermia: Mechanisms, Applications, and Future Perspectives

Blood–brain barrier (BBB) represents one of the main physiological barriers in terms of effective CNS drug delivery, which affects the treatment options of brain cancers and neurological diseases. In this context, this review focuses on the use of magnetic nano system (MNS) to induce hyperthermia for modulating the BBB permeability. Here, we describe the mechanisms of controlled thermal elevation by magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) for BBB disruption. Important mechanisms include modulation of endothelial tight junctions, especially claudin‐5 and occludin, and enhanced transcellular transport through transcytosis pathways, often mediated by specific signaling cascades such as the RhoA/ROCK pathway and calcium fluxes. The review also points out the importance of polymeric coatings on nanocarriers for controlled loading and triggered release of pharmaceutical ingredients like chemotherapy agents and monoclonal antibodies. Preclinical data show the potential of MNS‐mediated hyperthermia to improve CNS delivery of multiple therapeutics. The review also discusses the key aspects for optimizing thermal dose, biocompatibility, target specificity, and future perspectives for clinical translation. This approach offers a promising way to overcome the limitations of the BBB and further therapeutic interventions for the CNS.