Targeting Multilayered Metabolic Networks in Brain Diseases: Emerging Perspectives on Nanodelivery Strategies.

Brain metabolism is uniquely regulated, and alterations in its metabolic networks often serve as critical drivers of the onset and progression of brain diseases. Therapeutic strategies that target these metabolic changes are regarded as fundamental to disease intervention. In complex metabolic networks, multi-level metabolic dysregulation typically initiates a shared pathological process: the disruption of core cell metabolism leads to impaired cell-cell interactions, ultimately promoting the development of a malignant microenvironment that supports disease progression. This process encompasses complex mechanisms such as substance transport, cell signaling, and the dynamic regulation of the microenvironment. Smart nanodelivery systems, with their versatility, responsiveness, and modularity, can precisely modulate these dynamic metabolic networks in brain diseases, guided by the underlying pathological mechanisms. In this review, the metabolic network characteristics associated with brain diseases is summarized and the use of nanodelivery systems and their combinations are explored for metabolic regulation, aiming to establish a novel therapeutic paradigm.