Abstract
It has been indicated that doxorubicin (Dox) can induce some unwanted cardiotoxicity through different signaling pathways. In the present study, calycosin-PEG-PPG-PEG copolymer nanomicelles were developed and well-characterized by different techniques. Afterwards, the protective effects of calycosin-triblock copolymer nanomicelles against Dox-stimulated cardiotoxicity in H9C2 cardiomyocytes were explored by viability, reactive oxygen species (ROS), and reactive nitrogen species (RNS) assays. Also, the expression of ERp57, p53, Bax, and Bcl-2 at both mRNA and protein levels were assessed by qPCR and western blot , respectively. It was seen that synthesized calycosin-triblock copolymer nanomicelles had a size of around 20–30 nm with good colloidal stability, sustained drug release and improved dissolution rate. Also, it was shown that calycosin-triblock copolymer nanomicelles can mitigate Dox-induced cardiotoxicity through a remarkable reduction in ROS and RNS generation. Also, it was found that calycosin-triblock copolymer nanomicelles resulted in the downregulation of Bax and p53 and overexpression of Bcl-2 and ERp57 at both mRNA and proteins levels and these protective effects were inhibited in the presence of ERp57-siRNA silencing. Therefore, this study may provide useful information about the development of drug-loaded nanomicelles for mitigation of Dox-induced toxicity.
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