Rewiring Neuroimmunity: Nanoplatform Innovations for CNS Disease Therapy

Abstract Central nervous system (CNS) diseases pose a significant global health challenge, currently affecting one in six individuals worldwide. Despite extensive research into their molecular and cellular mechanisms, effective treatment remains elusive due to the inherent complexity of CNS disorders and the protective constraints of the blood‐brain barrier (BBB).Conventional monotherapies often fail to produce satisfactory outcomes. In recent years, nanomaterials have emerged as promising therapeutic platforms—offering enhanced pharmacokinetics, improved biodistribution, and reduced systemic toxicity. More importantly, multifunctional nanomaterials can be engineered to actively target the brain parenchyma and lesion sites, co‐deliver multiple therapeutics, and modulate neuroimmune responses synergistically. Their tunability and adaptability to diverse pathological contexts make them well‐suited to address the multifactorial nature of CNS diseases. This review discusses the mechanisms contributing to therapeutic resistance in common brain disorders and highlights the potential of engineered nanomaterials that can address the multifaceted disease microenvironment. We also identify current challenges and prospects for the rational design of multifunctional nanoplatforms tailored to CNS disease treatment.