2. Academic Validation
  3. Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression

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

  • J Nanobiotechnology. 2023 Aug 8;21(1):261. doi: 10.1186/s12951-023-02005-y.
Yue Hu # 1 2,  Min Zhao # 1 2,  Hui Wang # 3,  Yang Guo 1 2,  Xiaolan Cheng 1 2,  Tong Zhao 1 2,  Hanqing Wang 4,  Yafeng Zhang 5,  Yong Ma 6 7,  Weiwei Tao 8 9 10
Affiliations

Affiliations

  • 1 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.
  • 2 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
  • 3 School of pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
  • 4 School of pharmacology, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, China.
  • 5 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. orthozhang@sina.com.
  • 6 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. 260758@njucm.edu.cn.
  • 7 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China. 260758@njucm.edu.cn.
  • 8 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. taoww@njucm.edu.cn.
  • 9 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China. taoww@njucm.edu.cn.
  • 10 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China. taoww@njucm.edu.cn.
  • # Contributed equally.
PMID: 37553718 DOI: 10.1186/s12951-023-02005-y
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.

Keywords

Estrogen; Exosome; Nanogel; PACAP; Perimenopausal Depression.

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