Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.
F, L., J, H., Z, C., F, Z., L, X., N, L., M, G., H, Y., Z, L., & X, Z. (2026). Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.. International journal of nanomedicine. https://doi.org/10.2147/IJN.S600720
F L, J H, Z C, F Z, L X, N L, et al. Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.. International journal of nanomedicine. 2026; doi: 10.2147/IJN.S600720
F L, J H, Z C, et al. Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.[J]. International journal of nanomedicine. 2026. DOI: 10.2147/IJN.S600720.
@article{f2026,
author = {Lin F and Huang J and Chen Z and Zhong F and Xu L and Liu N and Gan M and Yin H and Li Z and Zhang X},
title = {Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.},
journal = {International journal of nanomedicine},
year = {2026},
doi = {10.2147/IJN.S600720},
note = {PMID: 42657388},
}
TY - JOUR AU - Lin F AU - Huang J AU - Chen Z AU - Zhong F AU - Xu L AU - Liu N AU - Gan M AU - Yin H AU - Li Z AU - Zhang X TI - Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress. T2 - International journal of nanomedicine PY - 2026 DO - 10.2147/IJN.S600720 AN - PMID:42657388 ER -
BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge in the management of acute myocardial infarction. Ginsenoside Rg1, a bioactive component from Panax ginseng, exhibits cardioprotective properties but suffers from poor bioavailability and limited tissue targeting. METHODS: We designed a novel DNA nanocarrier, Rg1@pTDN, by loading Rg1 onto a tetrahedral DNA nanostructure (TDN) modified with the myocardial-targeting peptide CREKA. The physicochemical characteristics of Rg1@pTDN were evaluated by DLS, zeta potential analysis, AFM, and gel electrophoresis. Biodistribution, biosafety, and cellular uptake were assessed in vitro and in vivo. Cardioprotective efficacy was evaluated in a murine MIRI model and a H/R injury cell model. Mechanistic studies focused on oxidative stress and endoplasmic reticulum (ER) stress pathways. RESULTS: Rg1@pTDN exhibited uniform nanoscale structure, high Rg1 loading efficiency, and good colloidal stability. In vivo imaging revealed preferential accumulation in cardiac tissue following intravenous administration. Rg1@pTDN was well tolerated and improved survival, cardiac function, and myocardial histology in MIRI mice. It significantly reduced serum CK-MB concentrations and oxidative stress markers (MDA), while increasing antioxidant enzyme activities (SOD, GSH-Px). In vitro, Rg1@pTDN suppressed ROS accumulation and H/R-induced apoptosis in H9c2 cells. Furthermore, Rg1@pTDN alleviated H/R-induced ER stress, as shown by decreased GRP78 and CHOP mRNA expression and reduced phosphorylated PERK and CHOP protein levels. CONCLUSION: Rg1@pTDN represents a promising nanotherapeutic strategy for myocardial ischemia-reperfusion injury through targeted delivery and dual inhibition of oxidative and ER stress. This DNA-based platform offers a versatile approach for enhancing the efficacy of natural compounds in cardiovascular disease.