Erythrocyte membrane-camouflaged doxorubicin nanoparticles for enhancing therapeutic efficacy in primary liver cancer

Doxorubicin (DOX), an anthracycline antibiotic, stands as one of the most potent and clinically ubiquitous chemotherapeutic agents for cancer treatment. Despite advances in clinical supportive care, strategies to prevent DOX-induced toxicity remain inadequate – with cardiotoxicity being a particularly devastating complication that can progress to heart failure. To address this unmet need, we engineered a novel core–shell biomimetic nanoparticle (NP) camouflaged with erythrocyte membranes, tailored for the targeted delivery of DOX to treat liver cancer while mitigating DOX-induced cardiotoxicity. This erythrocyte membrane-camouflaged biomimetic NP system exhibits an average diameter of 262.4 nm – an optimal size for prolonged systemic circulation – and possesses exceptional biocompatibility, coupled with enhanced responsiveness to the acidic tumour microenvironment. These synergistic features collectively augment the anti-tumour efficacy of DOX against hepatocellular carcinoma (HCC). Our findings highlight that the erythrocyte membrane-camouflaged NP serves as a promising biomimetic nanocarrier: it enables efficient delivery of chemotherapeutics to tumour sites while attenuating their off-target side effects (e.g. DOX-induced cardiotoxicity). This work thus provides a valuable strategy for improving the therapeutic index of anthracycline-based cancer treatments.