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

## TL;DR

This review explores how brain diseases involve complex metabolic disruptions and how smart nanodelivery systems can precisely target these changes for treatment.

## Contribution

The paper introduces a systems-level framework combining metabolic logic and nanomedicine for targeted brain disease therapy.

## Key findings

- Multilayered metabolic dysregulation in brain diseases leads to impaired cell interactions and malignant microenvironments.
- Smart nanodelivery systems can modulate dynamic metabolic networks based on pathological mechanisms.
- Nanodelivery strategies offer a novel therapeutic paradigm for reprogramming brain disease metabolism.

## Abstract

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.

Brain diseases involve multilayered metabolic disruptions that reshape cellular interactions and microenvironments. This review outlines core metabolic features across disease states and presents emerging nanodelivery strategies as precision tools to reprogram pathological metabolism. By bridging metabolic logic and smart nanomedicine, it offers a systems‐level framework for targeted therapeutic intervention in the brain.