DNA binding graphene quantum dots inhibit dual topoisomerases for cancer chemotherapy

DNA-protein interfacial inhibition is a classical paradigm for design of diverse interfacial inhibitors as clinically relevant anticancer drugs. To extend this paradigm from small molecules to nanoparticles, we synthesized pyridine N-modified polycationic graphene quantum dots (Graphenin) as a new class of DNA probes and interfacial inhibitors for cancer chemotherapy. Compared with classical interfacial inhibitors, Graphenin showed enhanced interfacial inhibition against Topoisomerase I and II, both of which are clinically important targets for chemotherapy. The enhanced interfacial inhibition activity was ascribed to their distinct DNA targeting capability preferentially at the DNA major groove, through which many DNA binding proteins recognize DNA. They induced DNA damage and cell apoptosis for sensitive and resistant cancer cell lines, and great potential for tumor chemotherapy was demonstrated in vitro and in vivo . Our results have identified shape-complementary Graphenin as the first DNA major groove binder to inhibit DNA binding enzymes for chemotherapy. Overall scheme to show the design of polycationic GQDs (Graphenin) as the first MAG binding nanomedicine to confer pharmacological activities by enhanced interfacial inhibition of Topo-I and Topo-II enzymes.