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外泌体囊泡包裹的 ROS 响应性纳米凝胶改善围绝经期抑郁症的靶向治疗

Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression.

机构信息

Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, 8 Zhongnan West Road, Wuxi, 214071, China.

School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.

出版信息

J Nanobiotechnology. 2023 Aug 8;21(1):261. doi: 10.1186/s12951-023-02005-y.

DOI:10.1186/s12951-023-02005-y
PMID:37553718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10408189/
Abstract

The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.

摘要

天然膜作为纳米粒子穿越血脑屏障 (BBB) 的涂层的发展为治疗中枢神经系统 (CNS) 疾病提供了一种有效方法。在这项研究中，我们设计了一种负载 PACAP 和雌激素 (E2) 的纳米凝胶，用外泌体包裹，并对活性氧 (ROS) 做出响应，记为 HA NGs@exosomes。这种新设计的目的是作为一种有效的药物载体，用于治疗围绝经期抑郁症的靶向治疗。体外和体内实验均证明了 HA NGs@exosomes 的高效细胞摄取和 BBB 穿透能力。经鼻内给予 HA NGs@exosomes 干预后，慢性不可预测轻度应激 (CUMS) 下的去卵巢小鼠表现出行为表现的改善，表明 HA NGs@exosomes 产生了快速起效的抗抑郁作用。此外，HA NGs@exosomes 表现出显著的抗氧化和抗炎特性，并可能调节 PACAP/PAC1 途径中的关键蛋白表达，以促进突触可塑性。我们的结果为 ROS 响应性纳米凝胶包被的外泌体作为治疗围绝经期抑郁症的有前途的药物载体的应用提供了概念验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/ae44f836282e/12951_2023_2005_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/b1cc7bc49deb/12951_2023_2005_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/4173390194c8/12951_2023_2005_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/a711bc658c99/12951_2023_2005_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/93bd7b3141c8/12951_2023_2005_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/e5ca7333d195/12951_2023_2005_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/648659c2dc4e/12951_2023_2005_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/ae44f836282e/12951_2023_2005_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/b1cc7bc49deb/12951_2023_2005_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/99ed91ade253/12951_2023_2005_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/a06b066e2c8c/12951_2023_2005_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/4173390194c8/12951_2023_2005_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/a711bc658c99/12951_2023_2005_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/93bd7b3141c8/12951_2023_2005_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/e5ca7333d195/12951_2023_2005_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/648659c2dc4e/12951_2023_2005_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a3/10408189/ae44f836282e/12951_2023_2005_Fig9_HTML.jpg

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