Metal ions-mediated self-assembly of nanomedicine for combinational therapy against triple-negative breast cancer

Carrier-free drug delivery systems based on drug self-assembly could improve systemic safety by avoiding the use of pharmaceutical excipients. It has become a feasible way to accelerate the clinical transformation of nano-formulations. For the combinational treatment of triple-negative breast cancer (TNBC), we developed a ferrous ions-mediated self-assembly nanomedicine ([email protected]), consisting of a chemotherapeutic agent (doxorubicin, DOX), Chinese herbal medicinal ingredient (quercetin) and RBC biomimetic membrane. It was found to have high drug loading capacities in [email protected], which was 31.93% for DOX and 31.89% for quercetin, respectively. As an active Chinese herb ingredient, quercetin could alleviate the cardiotoxicity of DOX, owing to its powerful antioxidant capacity. Benefited from the effective synergistic effect among DOX, quercetin and Fe2+, [email protected] could induce apoptosis of cancer cells effectively through mitochondrial damaging pathway and autophagy-induced cell death. The accumulation of DOX at tumor sites was significantly improved by [email protected], which was 4.61-fold higher than free DOX administration. By combining the biological functions of each component, [email protected] could achieve enhanced antitumor efficacy and pulmonary metastasis inhibition in TNBC therapy.