Phytochemical-engineered vesicles offer breakthrough in myocardial ischemia/reperfusion therapy

As unresolved oxidative stress and inflammatory cascades critically exacerbate cardiomyocyte death and heart failure,myocardial ischemia-reperfusion injury (MI/RI) represents a significant challenge in the treatment of acute myocardial infarction. Although mesenchymal stromal cells (MSCs) show great promise in terms of their immunomodulatory and regenerative potential, their clinical translation is constrained by poor in vivo survival, inefficient targeting, and scalability challenges. Conventional MSC therapies depend on paracrine signalling via extracellular vesicles (EVs). However, native EVs are characterised by limitations in terms of yield and stability. Emerging strategies, such as bioactive compound priming of MSCs or nanoengineering artificial cell-derived vesicles (ACDVs), aim to bridge this gap by combining biological potency with scalable manufacturing. However, the role of phytomedicine-enhanced nanovesicles in mitigating MI/RI remains underexplored.

A team of biomedical engineers and pharmacologists led by Jing-Yu Wang and Chun Li from Beijing University of Chinese Medicine has pioneered a breakthrough in nanovesicle therapy. By priming MSCs with Ginsenoside Rg1—a bioactive compound from Panax ginseng—and employing serial extrusion technology, they engineered high-performance Rg1-activated ACDVs (Rg1-ACDVs). These nanovesicles demonstrated dual efficacy in scavenging mitochondrial reactive oxygen species (ROS) and repairing DNA damage, significantly reducing infarct size and restoring cardiac function in animal models. Their findings, published in Nano Research on May 2025 under the title *“Artificial Cell Derived Vesicles from Ginsenoside Rg1-Primed Mesenchymal Stromal Cells Mitigate Oxidative Stress and DNA Damage in Myocardial Ischemic/Reperfusion Injury”*, mark a leap toward clinical translation of plant-empowered regenerative nanomedicine.

The team published their research article in Nano Research on May 29, 2025.

“Our work establishes Rg1-ACDVs as a paradigm-shifting strategy,” said Jing-Yu Wang, corresponding author , Beijing University of Chinese Medicine. “Unlike conventional EVs, Rg1-ACDVs combine Ginsenoside Rg1 priming with nanoscale engineering and introduces Rg1-ACDVs as a scalable and innovative strategy, offering a promising approach for improving clinical outcomes in MI/RI therapy.” Dr. Wang emphasized that the team’s extrusion-based extrusion platform achieves 10-fold higher yield than traditional EV isolation methods, overcoming critical bottlenecks in nanotherapeutics manufacturing.

Multi-omics profiling revealed that, in comparison with Rg1-EVs, Rg1-ACDVs exhibited an increased expression of proteins and nucleic acids associated with mitochondria and DNA repair. These molecular signatures were imprinted into ACDVs. In rodent models of MI/RI, the injection of Rg1-ACDVs has been shown to reduce reactive oxygen species (ROS) levels and suppress DNA damage markers (γ-H2AX and 8-OHdG). These effects have been demonstrated to result in a significant improvement in left ventricular ejection fraction.

Chun Li, co-corresponding author, added that future research would focus on multiplexed engineering, namely the combination of Rg1 with other phytochemicals to target inflammatory pathways, and the integration of smart targeting ligands for enhanced cardiac specificity.

The following individuals have made contributions to this project: Shuang Zhao, Huilan Fan, Shuxiang Yang, Chengyan Xu, Yanli Liu, Yixuan Guo, Yangyi Yu, Yafei Sun, Haijing Li, Jincheng Guo (all from the Beijing University of Chinese Medicine) and Yong Wang (from Dongzhimen Hospital, Beijing University of Chinese Medicine).

The financial resources for this project were provided by two entities: the National Natural Science Foundation of China (No. 82222075) and the Starting Grants for Young Talents of Beijing University of Chinese Medicine.

About the Authors

Jingyu Wang is an associate professor at Beijing University of Chinese Medicine. She is mainly engaged in the research of extracellular vesicles of active ingredients of combined traditional Chinese medicine for the treatment of cardiovascular diseases.

Chun Li is a professor at Beijing University of Chinese Medicine. She mainly engaged in pharmacological research on the prevention and treatment of cardiovascular diseases with traditional Chinese medicine.

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.