Abstract
Depression, as a highly prevalent psychiatric disorder, has emerged as a global public health challenge. Its pathological mechanisms involve the cross-regulation of multiple pathways, including neurotransmitter imbalance, neuroinflammation, and oxidative stress. Conventional oral antidepressants are limited in clinical application due to low blood-brain barrier penetration, significant side effects, and restricted therapeutic response rates. In recent years, drug delivery nanosystems (DDNs) have achieved precise regulation and repair of the pathological processes underlying depression through various functional modification strategies, such as targeted conjugation, stimuli responsiveness, and biomimetic simulation. Future efforts should focus on promoting their clinical translation via multi-functional integration, optimization of intelligent response mechanisms, and interdisciplinary collaboration. This review systematically summarizes the major pathogenic pathways of depression, as well as the mechanisms of action and research progress of functionalized DDNs in alleviating depression by targeting and remodeling key pathogenic pathways. It provides theoretical and technical references for the precise treatment of depression and the development of precision medicine for psychiatric disorders.