Haizhou Pan,1,* Qianxi Ye,1,* Yifan Li,2 Liang Ma,1 Yiming Ni1 

1Department of Cardiovascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Orthopedics, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yiming Ni, Department of Cardiovascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, People’s Republic of China, Tel +86-0571-87236348, Email 1183020@zju.edu.cn

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.

Keywords: doxorubicin-induced cardiotoxicity, tetrahedral framework nucleic acids, mitochondria, oxidative stress, apoptosis