Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury.
P, Q., J, S., X, L., Y, G., J, L., H, Z., M, Z., C, M., X, L., & W, T. (2026). Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury.. Theranostics. https://doi.org/10.7150/thno.123209
P Q, J S, X L, Y G, J L, H Z, et al. Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury.. Theranostics. 2026; doi: 10.7150/thno.123209
P Q, J S, X L, et al. Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury.[J]. Theranostics. 2026. DOI: 10.7150/thno.123209.
@article{p2026,
author = {Qu P and Shi J and Li X and Gu Y and Liu J and Zhang H and Zhou M and Ma C and Li X and Tian W},
title = {Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury.},
journal = {Theranostics},
year = {2026},
doi = {10.7150/thno.123209},
note = {PMID: 42370197},
}
TY - JOUR AU - Qu P AU - Shi J AU - Li X AU - Gu Y AU - Liu J AU - Zhang H AU - Zhou M AU - Ma C AU - Li X AU - Tian W TI - Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury. T2 - Theranostics PY - 2026 DO - 10.7150/thno.123209 AN - PMID:42370197 ER -
The pathogenesis of myocardial ischemia-reperfusion (MI/R) injury is intricately linked to mitochondrial dysfunction occurring during both the ischemic and reperfusion phases. Through single-cell transcriptome analysis, we identified a subpopulation of HEY1-high expressing cardiomyocytes (HEY1+ CMs) characterized by superior mitochondrial homeostasis. To leverage this, we isolated P5CS-type or ATP5B-type functional mitochondria from a ΔΨm-high subpopulation, which was obtained via membrane potential sorting following dual overexpression in HEY1+ CMs, and subsequently encapsulated them within HEY1+ CM-derived exosomes to achieve stable, targeted delivery. We designed a responsive microneedle patch based on local copper/iron ion dynamics to enable the stage-specific release of these mitochondria within the ischemic or reperfusion microenvironments. In a Bama minipig MI/R model, this system significantly ameliorated cardiac function, reduced infarct size, and attenuated cardiomyocyte death. Mechanistically, the therapeutic strategy enhanced mitochondrial structural integrity and energy metabolic function. This study establishes a responsive, stage-specific mitochondrial delivery platform, offering a promising strategy for the precision treatment of ischemic heart disease.