Key result
Liposomal simvastatin-doxorubicin cuts cardiomyocyte ROS and zebrafish cardiotoxicity while boosting cancer cytotoxicity.
Why the study?
Doxorubicin is limited by cardiotoxicity, and while liposomal doxorubicin helps it does not surpass unencapsulated drug efficacy, leading researchers to explore whether co-encapsulation with cardioprotective simvastatin improves safety and anticancer activity.
Does liposomal co-encapsulation of simvastatin and doxorubicin reduce cardiotoxicity while retaining anti-cancer efficacy in preclinical models?
Does liposomal co-encapsulation of simvastatin and doxorubicin reduce cardiotoxicity while retaining anti-cancer efficacy in preclinical models?
Liposomal co-encapsulation of simvastatin and doxorubicin represents a promising strategy to reduce anthracycline-induced cardiotoxicity while potentiating anti-cancer efficacy in preclinical models.
Should not yet change doxorubicin regimens; leaves open whether liposomal simvastatin co-encapsulation reduces cardiotoxicity in patients.
Anthracyclines such as doxorubicin (Dox) are the preferred chemotherapeutics for several cancers. However, Dox-induced cardiotoxicity limits its therapeutic potential. Liposomal encapsulation of Dox has been used for patients with risk to develop Dox induced cardiotoxicity but does not surpass the efficacy of the unencapsulated drug. Statins are widely used as cholesterol lowering drugs and have also demonstrated cardioprotective activity in cancer patients undergoing Dox therapy. We developed a liposome loaded with Dox and simvastatin (Sim) and investigated their effect on cardiomyocytes and zebrafish larvae. Furthermore, we investigated if the doses required for cardioprotection compromised the cytotoxicity of Dox in mammary and prostate cancer cells. Combination of Sim and Dox reduced ROS generation in cardiomyocytes, both given as free drugs, or co-encapsulated in liposomes. In contrast, Sim potentiated ROS-generation and cytotoxic activity of Dox towards cancer cells also when co-encapsulated in liposomes. In zebrafish larvae, Sim treatment reduced Dox-induced cardiac affection, and the liposomes did not induce any sign of Dox-induced cardiotoxicity. Our results show that liposomal co-encapsulation of Sim and Dox can be an efficient way of further reducing the risk of cardiotoxic events of liposomal Dox, while retaining, or even potentiating the anti-cancer effect of Dox.
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Bjørnstad et al. (2022) studied Doxorubicin-induced cardiotoxicity and cancer. Liposomal doxorubicin and simvastatin vs. Free drugs or doxorubicin alone was evaluated on ROS generation in cardiomyocytes, cytotoxicity in cancer cells, and cardiac affection in zebrafish larvae. Liposomal co-encapsulation of simvastatin and doxorubicin reduced ROS generation in cardiomyocytes and cardiac affection in zebrafish larvae while potentiating cytotoxicity towards cancer cells.
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