In vivo self-degradable graphene nanomedicine operated by DNAzyme and photo-switch for controlled anticancer therapy

Although graphene oxide (GO) possesses many beneficial functionalities for biomedical usage as itself, modification of GO surface with several polymers or protein is inevitable for in vivo applications; however, such modification limits the degradability of GO due to the steric hindrance. In that context, designing of a surface modified GO carrier that is going to be degraded after its biological function (i.e., drug delivery) is highly desired, especially at complex in vivo level. Herein, we design an unprecedented catalytic GO nanomedicine by applying the catalytic DNA, achieving self-degradation of GO in systemic level in the body after the therapy following surface modification. Once the catalytic GO nanomedicines are taken up by mucin1 (MUC1) aptamer-facilitated endocytosis, a photo-switch triggers the release of doxorubicin from the DNA. The single stranded G-quadruplex sequence on the surface of GO forms a quartet structure and becomes DNAzyme by binding with hemin on the GO surface, exhibiting peroxidase effect. Due to the high H2O2 concentration in cancer cells, the catalytic GO nanomedicine generates sufficient amount of strong oxidant, hypochlorous acid (HOCl), inducing GO degradation into small fragments for potential clearance. We demonstrate the potential of our catalytic GO nanomedicine for both therapy and degradation at cellular and complex in vivo environment.