Nanomedicine strategies for mitigating cancer therapy-related cardiovascular toxicity

Cancer therapy-induced cardiotoxicity represents a serious clinical complication driven by oxidative injury, topoisomerase IIβ-mediated DNA damage, endoplasmic reticulum (ER) stress, mitochondrial dysfunction and sustained inflammatory signalling. These pathogenic processes can lead to a range of adverse outcomes, including myocarditis, vascular and valvular alterations, myocardial fibrosis, electrophysiological remodelling and related cardiac abnormalities. A growing body of experimental evidence indicates that nanocarriers can markedly reduce unintended cardiac exposure to cytotoxic agents. These systems exploit the enhanced permeability and retention (EPR) effect in the tumour microenvironment while lowering free drug concentrations in the myocardium. Progress in targeting strategies, spanning surface-functionalised ligands and antibodies to stimuli-responsive nanoparticles, further constrains off-target distribution and enables spatially controlled drug release at the tumour site. In parallel, nanoparticles co-loaded with cardioprotective agents, including antioxidants, Top2β inhibitors, small molecules and selected natural products, demonstrate additive benefits by intercepting central mediators of cardiomyocyte injury. Such dual co-delivery platforms may also augment antitumour efficacy. Nanocarriers incorporating these cardioprotective agents may similarly attenuate radiotherapy-induced cardiotoxicity. This review critically evaluates these multifaceted nanomedicine strategies and outlines a comprehensive roadmap for harnessing nanoparticle technologies to prevent and mitigate cardiotoxicity associated with cancer therapy.