Hollow mesoporous Prussian blue nanozymes alleviate doxorubicin-induced cardiotoxicity by restraining oxidative stress associated with Nrf2 signaling

Doxorubicin-induced cardiomyopathy (DIC) is a toxic side effect that cannot be ignored during chemotherapy for malignant tumors. In this work, we synthesized a novel nano-chemotherapeutic drug based on Prussian blue nanozyme to alleviate DIC. Hollow mesoporous Prussian blue (HmPB) nanoparticles were used as a carrier to load doxorubicin (DOX) through electrostatic adsorption and obtain a novel chemotherapy drug, HmPB(DOX). In vivo and in vitro chemotherapy efficacy and acute toxicity evaluation experiments were conducted. The results suggest that HmPB(DOX) exhibits pH-responsive characteristics and minimizes the release of DOX from within HmPB(DOX) in cardiomyocytes. However, in the acidic tumor microenvironment, the release of DOX from HmPB (DOX) is notably enhanced. More importantly, HmPB(DOX) possesses excellent antioxidant enzyme activity, effectively clearing DOX-induced reactive oxygen species (ROS) and alleviating oxidative stress in cardiomyocytes. Doxorubicin is pivotal in the chemotherapy of malignant tumors. This study presents novel insights for mitigating the toxic and side effects of DOX, offering new strategies to enhance tolerance to chemotherapy.