Doxorubicin-Induced Toxicity and Bisoprolol-Protective Efficacy for Cardiomyocytes Monitored by Scanning...

Cardiotoxicity from chemotherapy drugs is a major adverse effect of cancer chemotherapy, which strongly compromises therapeutic outcomes. The application of cardioprotective agents is an effective strategy to mitigate cardiotoxicity in the clinic. However, the effects of chemotherapeutic drugs and their doses, as well as the efficacy of cardioprotective agents on the function of cardiomyocytes, especially at different stages of cardiotoxicity, have not been well explored, partly owing to the lack of real-time functional parameters of cardiomyocytes after drug treatment. Herein, we constructed in vitro doxorubicin (DOX)-induced cardiotoxicity (DIC) models through culturing neonatal rat primary cardiomyocytes on polyacrylamide (PA) gels with a stiffness of around 20.0 kPa, and adding DOX at different concentrations to mimic the mild, moderate, and severe stages of chemotherapeutic drug-induced cardiotoxicity. We used scanning electrochemical microscopy (SECM) to monitor the respiratory activity, contraction frequency, and membrane permeability of cardiomyocytes after DOX treatment in situ. The SECM results obtained demonstrated that 0.25-5.0 μM DOX dosages led to decreased respiratory activity and contraction frequency, accompanied by increased membrane permeability of cardiomyocytes. We also used SECM to evaluate the cardioprotective effect of bisoprolol (a clinically approved β-blocker for cardiovascular diseases) on cardiomyocytes under DOX treatment and obtained its optimal protective efficacy for 1.0 μM DOX-treated cardiomyocytes. Our work provides in situ functional information on living cardiomyocytes under chemotherapeutic drug and cardioprotective agent treatments, contributing to a better understanding of the pathological features and prevention strategies of chemotherapy-induced cardiotoxicity.