Tetrahedral Framework Nucleic Acids Inhibit Oxidative Stress and Cardiomyocyte Apoptosis in Doxorubicin-Induced Cardiotoxicity.

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.