作者：

Fuwei Qi^1,2, Yinsheng Liao^2,3#, Chenglong Ge⁴, Yiyao Yang⁴, Junliang Zhu⁴, Jiang Zhu¹*, Yang Zhou⁴*, Hong Xie¹*, and Lichen Yin⁴*.

单位：

¹Department of Anesthesiology, the Second Affiliated Hospital of Soochow University, Suzhou, 215002, China.

²Department of Anesthesiology, the First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, Suzhou, 215400, China.

³Suzhou Medical College of Soochow University, Suzhou, 215123, China.

⁴Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.

摘要：

The disruption of mitochondrial homeostasis in neurons accounts for the onset and progression of postoperative cognitive dysfunction (POCD). Echinacoside (ECH) can facilitate mitochondrial fusion to mediate neuroprotection, but its therapeutic efficacy is greatly limited by inefficient brain accumulation and neuronal delivery. Herein, ECH-encapsulated micelles are constructed from the copolymer containing the poly(carboxybetaine methacrylate) (PCBMA) block and phenylboronic acid (PBA)-modified poly(dimethylamino)ethyl methacrylate block, which mediates effective, brain-targeted delivery via intranasal administration. In POCD mice, the micelles efficiently penetrate nasal mucosa via the betaine structure in PCBMA that can be recognized by betaine-GABA transporter 1 (BGT-1) on nasal epithelial cells, followed by the accumulation into the hippocampus through the submucosal olfactory and trigeminal nerve pathways. Subsequently, the micelles are efficiently internalized by neurons via BGT-1-mediated endocytosis. The over-produced reactive oxygen species inside neurons trigger micelles dissociation and ECH release, thereby inducing mitochondrial fusion to enhance neuron survival, ameliorate cerebral microenvironment, and restore cognitive and memory functions. This study reports a non-invasive strategy to overcome the physiological barriers against cerebral drug delivery and renders profound implications for POCD treatment.

影响因子：

18.5

分区情况：

一区

链接：

https://doi.org/10.1002/adfm.202505499