Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis.
X, G., X, L., J, Y., M, Y., P, S., K, L., Y, M., K, Z., Y, Z., & J, G. (2026). Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis.. International journal of nanomedicine. https://doi.org/10.2147/IJN.S611321
X G, X L, J Y, M Y, P S, K L, et al. Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis.. International journal of nanomedicine. 2026; doi: 10.2147/IJN.S611321
X G, X L, J Y, et al. Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis.[J]. International journal of nanomedicine. 2026. DOI: 10.2147/IJN.S611321.
@article{x2026,
author = {Guan X and Li X and Yang J and Yang M and Sun P and Li K and Ma Y and Zeng K and Zhao Y and Gao J},
title = {Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis.},
journal = {International journal of nanomedicine},
year = {2026},
doi = {10.2147/IJN.S611321},
note = {PMID: 42445825},
}
TY - JOUR AU - Guan X AU - Li X AU - Yang J AU - Yang M AU - Sun P AU - Li K AU - Ma Y AU - Zeng K AU - Zhao Y AU - Gao J TI - Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis. T2 - International journal of nanomedicine PY - 2026 DO - 10.2147/IJN.S611321 AN - PMID:42445825 ER -
PURPOSE: Myocardial microvascular injury plays a critical role in myocardial ischemia‑reperfusion injury (MI/RI), and ferroptosis has emerged as an important contributor to cardiac damage. Although Schizandrin A (Sch) possesses cardioprotective effects, its clinical application is limited by poor stability and low bioavailability. This study aimed to develop a CMEC‑targeted delivery system for Sch and evaluate its ability to attenuate ferroptosis in cardiac microvascular endothelial cells (CMECs), thereby alleviating MI/RI. METHODS: A cardiac endothelium‑targeting peptide CRPPR was conjugated to DSPE‑PEG2000 to prepare a Sch‑loaded nanoparticle (CRPPR@Sch). MI/RI was induced in mice by 45‑minute ischemia followed by 6‑hour reperfusion. CRPPR@Sch, free Sch, or non‑targeted DSP@Sch was administered intravenously for seven consecutive days. Cardiac function, infarct size, microvascular integrity and ferroptosis‑related markers were evaluated in vivo. In vitro, CMECs were exposed to hypoxia/reoxygenation (H/R), and ferroptosis was assessed. RESULTS: CRPPR@Sch efficiently accumulated in cardiac endothelial cells, improved cardiac function, reduced infarct size, restored microvascular perfusion, and alleviated CMEC injury. RNA‑seq indicated that CRPPR@Sch suppressed ferroptosis‑related pathways. In vitro and in vivo experiments demonstrated that CRPPR@Sch significantly up‑regulated GPX4 expression, reduced ROS, lipid peroxidation and ferroptosis markers. Moreover, TRIM25 expression was elevated in MI/RI mice and H/R‑injured CMECs. Co‑immunoprecipitation and molecular dynamics simulations revealed that Sch binds to GPX4 and interferes with TRIM25‑mediated GPX4 ubiquitination and degradation. CONCLUSION: CRPPR@Sch effectively delivers Sch to cardiac endothelium, stabilizes GPX4 by disrupting the TRIM25‑GPX4 interaction, and thus inhibits ferroptosis in CMECs, ultimately protecting against myocardial microvascular injury in MI/RI.