Cation−π Interaction-Mediated Copper-Based Nanoplatforms for Synergistic Chemodynamic–Chemotherapy with Enhanced Anticancer Efficacy

Chemodynamic therapy (CDT) is an emerging cancer treatment approach by generating hydroxyl radicals (·OH) that are toxic to tumor cells. However, it is limited by the instability of active metal catalysts and insufficient intracellular H₂O₂ levels. Here, we utilized and designed a system where cation-π interactions could address the former limitation by enriching, transforming, and stabilizing Cu⁺ on graphene oxide quantum dot (GOQD) surfaces, thereby promoting efficient Cu⁺-mediated Fenton-like reactions. To complement the latter, doxorubicin (DOX) was co-delivered: beyond its chemotherapeutic action, DOX elevated intracellular H₂O₂, supplying additional substrates for CDT. These mechanisms were integrated in a rod-shaped multifunctional nanoplatform(RMSN-NH₂-GOQD@DOX-Cu), which also afforded pH-temperature-responsive DOX release and enhanced cellular uptake. In vitro results demonstrated markedly improved anticancer efficacy (71.4%), substantially exceeding the additive effects of CDT (21.9%) and chemotherapy (37.3%) alone. This work highlighted cation-π interaction engineering as a practical route to stabilize active metal species within drug delivery systems and to potentiate CDT efficacy when combined with chemotherapeutic reagents, providing a generalizable strategy for synergistic cancer therapy.