Abstract
Doxorubicin (DOX) is a chemotherapeutic agent that can cause cardiotoxicity leading to progressive, chronic, life-threatening cardiomyopathy, called DOX-induced cardiomyopathy (DIC). DIC is a fatal cardiomyopathy with a worse prognosis compared to other cardiomyopathies and limits the use of DOX in malignancies due to its cardiotoxicity. DIC has been proven to be associated with reactive oxygen species (ROS)-induced side effect damage in cardiac myocytes. Currently, scavenging of reactive oxygen species is a practical strategy to reduce chemotherapy-associated DIC. Although quercetin has already been reported to have superior antioxidant activity, its clinical application is severely limited due to its rapid degradation and poor tissue absorption. Herein, we reported the preparation of a novel enzyme mimic via coordinated albumin, Zinc Ion (Zn(2+)) and quercetin. The enzyme mimics were capable of simultaneously increasing the biocompatibility and efficiently overcame the drawbacks of free quercetin, and were achieved by long circulation in vivo. Most importantly, these quercetin-based enzyme mimics had no effect on the antioxidant activity of quercetin. These beneficial therapeutic properties, together with high drug-carrying capacity and redox stimuli, will significantly improve quercetin's alleviation of chemotherapeutic cardiotoxicity without causing significant side effects. Therefore, nanoparticles of albumin-based Zn (II)-Quercetin have a promising clinical application as an effective agent for mitigating the cardiotoxicity of chemotherapy.