International journal of nanomedicine · 2026
Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.
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Lin Fengxia, Huang Jiamei, Chen Zetao, Zhong Fanjia, Xu Luhua, Liu Na, Gan Miao, Yin Haoran, Li Zhiwen, Zhang Xiaoduo, Song Yinzhi, Wang Xi, Zhuo Hui, Shang Hongcai, Lin Sheng, Zeng Zhicong, Yang Rongfeng
Аннотация
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.
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.