J Nanobiotechnology. 2026 Jul 3. doi: 10.1186/s12951-026-04772-w. Online ahead of print.
ABSTRACT
Despite advances in reperfusion therapy, treatment outcomes for myocardial infarction (MI) remain limited by poor targeting specificity and insufficient bioavailability of therapeutic agents in the ischemic myocardium. Here, we report CCTP-miR@CTP, a non-liposomal nanozyme platform that integrates cardiomyocyte-targeted delivery, intrinsic catalytic antioxidant activity, and therapeutic miRNA delivery within a single multifunctional system. In vitro, CCTP loaded with miR-26a mitigated H₂O₂-induced ROS accumulation, restored mitochondrial membrane potential, and suppressed autophagy and apoptosis in cardiomyocytes. In vivo, CCTP-miR@CTP preferentially accumulated in the infarcted myocardium, where it reduced infarct size, improved cardiac function, suppressed inflammatory responses, promoted angiogenesis, and attenuated extracellular matrix deposition and myocardial fibrosis. Mechanistically, CCTP not only served as an effective nucleic acid carrier but also coordinated redox homeostasis and cell survival pathways, amplifying the therapeutic efficacy of miRNA-based intervention. This study presents a material-design strategy to improve miRNA druggability in cardiovascular medicine and identifies CCTP-miR@CTP as a candidate nanotherapeutic for MI.
PMID:42399979 | DOI:10.1186/s12951-026-04772-w