Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial ischemia-reperfusion injury

Lan Li, Yili Wang, Rui Guo, Sheng Li, Jingyu Ni, Shan Gao, Xiumei Gao, Jingyuan Mao, Yan Zhu, Pingli Wu, Hongjun Wang, Deling Kong, Han Zhang, Meifeng Zhu, Guanwei Fan

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is a serious threat to the health and lives of patients without any effective therapy. Excessive production of reactive oxygen species (ROS) is considered a principal cause of MIRI. Some natural products, including ginsenoside Rg3 (Rg3), exhibit robust antioxidant activity. However, the lack of an effective delivery strategy for this hydrophobic compound hinders its clinical application. In addition, therapeutic targets and molecular mechanisms of Rg3 require further elucidation to establish its mode of action. This study aimed to generate ROS-responsive nanoparticles (PEG-b-PPS) via the self-assembly of diblock copolymers of poly (ethylene glycol) (PEG) and poly (propylene sulfide) (PPS) and use them for Rg3 encapsulation and delivery. We identified FoxO3a as the therapeutic target of Rg3 using molecular docking and gene silencing. In rat ischemia-reperfusion model, an intramyocardial injection of Rg3-loaded PEG-b-PPS nanoparticles improved the cardiac function and reduced the infarct size. The mechanism of action was established as Rg3 targeting of FoxO3a, which inhibited the promotion of oxidative stress, inflammation, and fibrosis via downstream signaling pathways. In conclusion, this approach, involving ROS-responsive drug release, together with the identification of the target and mechanism of action of Rg3, provided an effective strategy for treating ischemic diseases and oxidative stress and could accelerate the implementation of hydrophobic natural products in clinical applications.

Original languageEnglish
Pages (from-to)259-272
Number of pages14
JournalJournal of Controlled Release
Volume317
DOIs
StatePublished - 10 Jan 2020

Keywords

  • FoxO3a
  • Ginsenoside Rg3
  • Myocardial ischemia–reperfusion injury
  • ROS-responsive nanoparticles

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