Constructed transferrin receptor-targeted liposome for the delivery of fluvoxamine to improve prognosis in a traumatic brain injury mouse model

作者：Liang Mi, Jiangyuan Yuan, Yuxin Jiang, Yuqian Hu, Chuanxiang Lv, Yongqiang Xu, Mingqi Liu, Tao Liu, Xuanhui Liu, Jinhao Huang, Rongcai Jiang, Wei Quan · 发表于：Drug Delivery · 年份：2025 · DOI：10.1080/10717544.2025.2486840 · 被引用次数：14 · 研究领域：Cerebrospinal fluid and hydrocephalus、Traumatic Brain Injury and Neurovascular Disturbances、Neonatal and fetal brain pathology

The dysregulation of blood–brain barrier (BBB) activates pathological mechanisms such as neuroinflammation after traumatic brain injury (TBI), and glymphatic system dysfunction accelerates toxic waste accumulation after TBI. It is essential to find an effective way to inhibit inflammation and repair BBB and glymphatic system after TBI; however, effective and lasting drug therapy remains challenging because BBB severely prevents drugs from being delivered to central nervous system. Transferrin receptors (TfRs) are mainly expressed on brain capillary endothelial cells. Here, we report a TfR-targeted nanomedicine for TBI treatment by penetrating BBB and delivering fluvoxamine (Flv). The TfR-targeted polypeptide liposome loaded with Flv (TPL-Flv) implements cell targeting ability on human umbilical vein endothelial cells (HUVECs) in vitro detected by flow cytometry, and drug safety was proved through cell viability analysis and blood routine and biochemistry analysis. Afterwards, we established a controlled cortical impact model to explore TPL-Flv administration effects on TBI mice. We confirmed that TPL-Flv could stimulate CXCR4/SDF-1 signaling pathway, activate Treg cells, and inhibit inflammation after TBI. TPL-Flv treatment also alleviated BBB disruption and restored aquaporin-4 (AQP4) polarization, as well as reversed glymphatic dysfunction. Furthermore, TPL-Flv accomplished remarkable improvement of motor and cognitive functions. These findings demonstrate that TPL-Flv can ...