Abstract
Background: Doxorubicin-induced cardiotoxicity (DIC) is a major clinical limitation of doxorubicin therapy, driven by mitochondrial dysfunction and apoptosis. Tetrahedral framework nucleic acids (tFNAs), as novel 3D DNA nanostructures, exhibit antioxidative and anti-apoptotic properties, suggesting therapeutic potential for DIC. Methods: The therapeutic efficacy of tFNAs was evaluated through in vivo (mouse model) and in vitro (cardiac cell lines) experiments. Apoptotic pathways were analyzed via AKT/p53 signaling inhibition assays, while cardiac function was assessed by histological examination and biochemical analysis. Results: In vitro results demonstrated that tFNAs significantly attenuated DIC by suppressing AKT/p53-mediated apoptosis. In vivo studies confirmed functional improvement in cardiac tissue, validated by reduced biomarkers of cardiotoxicity and enhanced histological integrity. Conclusion: tFNAs effectively mitigated DIC pathogenesis through dual mechanisms of mitochondrial protection and apoptosis inhibition. These findings position tFNAs as a promising therapeutic strategy for clinical DIC management, warranting further translational studies.