Enhanced anticancer activity of graphene oxide quantum dot@Cu nanocomposites <i>via</i> cation–π interactions

Despite extensive efforts in the exploration of anticancer drugs, enhancing their anticancer activity and simultaneously overcoming drug resistance remains a challenge. Here, based on cation-π interactions, we prepared graphene oxide quantum dot@Cu (GOQD@Cu) nanocomposites and observed a transition in the valence state of copper ions from Cu²⁺ to Cu⁺ on the graphite surface. As a result, the anticancer activity of GOQD@Cu nanocomposites against HeLa cells exhibited a 2-fold and 1.6-fold enhancement compared to that of individual GOQD and Cu²⁺, respectively. This enhancement can be attributed to the high reactivity of Cu⁺ in the nanocomposites and the strengthened electrostatic interaction between the positively charged GOQD@Cu nanocomposites and negatively charged cell membranes. Furthermore, the treatment with GOQD@Cu nanocomposites significantly increased the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential (MMP). Additionally, enhanced anticancer activity was observed for other graphene-based materials with various cations (Fe³⁺, Zn²⁺ and K⁺). Our studies offer innovative insights for the design of novel nano-anticancer therapeutics.