Transferrin-modified carboxymethyl chitosan-chitosan nanoparticles as an efficient delivery carrier for targeted therapy of depression

• Published in: International journal of biological macromolecules 2025-01, Vol.286, p.138352, Article 138352
• Main Authors: He, Junhui, Yang, Li, Li, Dongmei, Xie, Jiaxiu, Zhou, Guili, Zhou, Rongfei, Li, Yi, Wei, Guining, Gong, Zhiqiang, Li, Li, Lai, Kedao, Zhou, Juying
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Nanocarriers; Transferrin
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.138352

Limitations of the blood-brain barrier (BBB) are responsible for the low efficacy and high toxicity of many antidepressants. However, strategies to enhance BBB targeting to improve the efficacy and safety of antidepressants remain challenging. In this study, we prepared transferrin (Tf)-functionalized chitosan (CS)-N,O-carboxymethy chitosan (NOCMS) nanosystems (NPs) (NOCMS-CS-Tf NPs), which can enhance BBB targeting in the depressive environment and allow more NPs to enter the brain. Experiments demonstrated that NOCMS-CS-Tf NPs had enhanced BBB targeting in the depressed environment compared to the normal environment and were safe and non-toxic. In vitro experiments demonstrated that NOCMS-CS-Tf NPs could target multiple cell lines in the brain and had stronger BBB targeting in neuroinflammatory and neuronal injury environments than in normal environments; in vivo experiments demonstrated that NOCMS-CS-Tf NPs had stronger BBB targeting in the brains of depressed mice than in normal mice, and were safe and non-toxic. The nanosystem enhanced BBB targeting in the setting of neuroinflammation and neuronal damage in depression, providing a promising approach to drug delivery systems for depression and bringing new hope for the return to the market of many first-line antidepressants that have been withdrawn. [Display omitted] •NOCMS-CS-Tf NPs is a non-toxic, biocompatible, BBB-targeting nanocarrier with a simple synthesis method.•The targeting of NOCMS-CS-Tf NPs exhibited enhanced BBB targeting in vivo and in vitro models of depression.•The NOCMS-CS-Tf NPs can be used to load active drugs for the treatment of brain diseases such as depression.