Nanomaterial-assisted epigenetic engineering of the blood–brain barrier: A dual strategy for drug delivery and permeability control

Recent advances at the interface of nanotechnology, epigenetics, and neurobiology have created new opportunities to address the blood–brain barrier (BBB), a major challenge in the treatment of central nervous system disorders. Two complementary strategies are gaining increasing attention: the epigenetic modulation of BBB permeability to enable transient and controllable changes in barrier function, and the use of nanomaterials as targeted carriers for epigenetic therapeutics. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA-mediated regulation, can influence genes involved in tight junction organization, endothelial transport, inflammatory signaling, and neurovascular repair. In parallel, rationally engineered nanocarriers may improve the stability, biodistribution, and brain delivery of epidrugs, nucleic acids, and programmable epigenome-editing systems, with performance strongly dependent on material composition, surface functionalization, targeting ligands, and release kinetics. This review discusses how epigenetic regulation and nanomedicine can be strategically integrated to modulate BBB function and improve therapeutic access to the brain. Particular attention is given to emerging strategies such as focused ultrasound mediated BBB modulation, intranasal delivery and CRISPR/dCas9-based epigenome editing, as well as to organoid models and spatial omics platforms that may facilitate translational BBB research. Together, these advances provide a framework for explore more controlled, reversible, and site-specific approaches to the delivery of epigenetic therapies to the central nervous system.