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5-羟色氨酸人工突触小泡穿越血脑屏障用于快速治疗抑郁症。

5-Hydroxytryptophan artificial synaptic vesicles across the blood-brain barrier for the rapid-acting treatment of depressive disorder.

作者信息

Chang Peng, Ma Jingwen, Li Ke, Wang Wei, Chen Dan, Liu Zhe, Zhan Wenhua, Zeng Yun, Zhan Yonghua

机构信息

School of Life Science and Technology, Xidian University and Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, 710126, PR China.

Medical Imaging Center, Ninth Hospital of Xi'an, Xi'an, 710054, PR China.

出版信息

Mater Today Bio. 2024 Nov 22;29:101357. doi: 10.1016/j.mtbio.2024.101357. eCollection 2024 Dec.

DOI:10.1016/j.mtbio.2024.101357
PMID:39659840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11629277/
Abstract

Conventional antidepressants are slow to work and have serious side effects and poor response rates. As a precursor to 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP) can be safely increased in concentration and rapidly metabolized into 5-HT in the brain, but the effectiveness of 5-HTP is severely limited due to its short half-life and lack of targeting. To traverse the blood-brain barrier (BBB) and achieve effective targeting, we designed a near-infrared (NIR) light-responsive artificial synaptic vesicles functionalized with an aptamer and loaded with 5-HTP and IR780. Photothermal approaches could improve the BBB permeability, and photothermal-triggered 5-HTP release could also be achieved. The ability to penetrate the BBB and enhance cerebral drug enrichment could be observed by fluorescence imaging. In addition, the nanoplatform incorporating the NIR laser considerably reduced depressive-like behaviors in chronic unpredictable moderate stress model mice in only 4 weeks, suggesting a potential approach for rapid-acting depression treatment.

摘要

传统抗抑郁药起效缓慢，副作用严重，有效率低。作为5-羟色胺（5-HT）的前体，5-羟色氨酸（5-HTP）可以安全地提高浓度，并在大脑中迅速代谢为5-HT，但由于其半衰期短且缺乏靶向性，5-HTP的有效性受到严重限制。为了穿越血脑屏障（BBB）并实现有效靶向，我们设计了一种近红外（NIR）光响应性人工突触小泡，其功能化有适配体，并装载有5-HTP和IR780。光热方法可以提高血脑屏障的通透性，还可以实现光热触发的5-HTP释放。通过荧光成像可以观察到穿透血脑屏障和增强脑内药物富集的能力。此外，结合近红外激光的纳米平台在仅4周内就显著减少了慢性不可预测中度应激模型小鼠的抑郁样行为，这表明这是一种快速治疗抑郁症的潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/2ae28c20b34d/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/2ae28c20b34d/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/0f884525d44c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/9897c3235e3e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/873aa40f1088/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/5dd1cfbe2d7e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/2e9d89a395d7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/3e332e54ea78/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/01f15e00559a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/b8e38758540d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20db/11629277/2ae28c20b34d/gr8.jpg

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