5FCN

5FCN is a bimetallic chitosan/hyaluronic acid nanoparticle designed for the therapy of triple-negative breast cancer (TNBC). It operates through a self-amplified dual mechanism involving ferroptosis and cuproptosis. The hyaluronic acid component of 5FCN specifically targets and binds to the overexpressed CD44 receptor on TNBC cells, facilitating receptor-mediated endocytosis. Upon cellular uptake and entry into acidic environments, the nanoparticles release Fe3+ and Cu2+ ions. These ions react with intracellular glutathione (GSH), leading to its depletion and compromising the cell's antioxidant defense system. The released Fe2+ and Cu+ then trigger Fenton/Fenton-like reactions with hydrogen peroxide (H2O2), generating highly toxic hydroxyl radicals (·OH) that promote ferroptosis. Simultaneously, the increasing levels of Cu+ induce lipoylated protein aggregation, which amplifies cuproptosis. In both in vitro and in vivo studies, 5FCN has demonstrated superior cell-killing efficacy against TNBC with minimal side effects, indicating its potential as a therapeutic agent.