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

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio Pub Date : 2024-11-22 DOI:10.1016/j.mtbio.2024.101357

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

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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.

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跨越血脑屏障的 5-羟色氨酸人工突触小泡用于抑郁症的速效治疗

传统的抗抑郁药物起效慢，副作用大，反应率低。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快速代谢为 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）光响应型人工突触囊泡，该囊泡由aptamer功能化，内含5-HTP和IR780。光热方法可以改善 BBB 的渗透性，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该药物穿透 BBB 的能力，并增强了脑药物富集。此外，结合了近红外激光的纳米平台仅用了4周就大大减少了慢性不可预知中度应激模型小鼠的抑郁样行为，这表明这是一种潜在的速效抑郁症治疗方法。

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来源期刊

Materials Today Bio Multiple-

CiteScore

8.30

自引率

4.90%

发文量

303

审稿时长

30 days

期刊介绍： Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).