Incorporation of Graphene Quantum Dots, Iron, and Doxorubicin in/on Ferritin Nanocages for Bimodal Imaging and Drug Delivery

Graphene quantum dots (GQDs) have been emerging as next-generation bioimaging agents because of their intrinsic strong fluorescence, photostability, aqueous stability, biocompatibility, and facile synthesis. In this work, GQDs are encapsulated in ferritin protein nanocages to develop multi-functional nanoplatforms toward multi-modal imaging and cancer therapy. Encapsulation of ultra-small GQDs is expected to reduce their quick excretion from the body and increase their bioimaging efficiency. To expand the functionality of protein nanocages as multi-modal imaging nanoprobes capable of both fluorescence and magnetic resonance imaging (MRI), GQDs and iron are encapsulated inside the core of AfFtn-AA (an engineered ferritin nanocage derived from the archaeon Archaeoglobus fulgidus). The co-encapsulation is achieved through an iron-mediated, self-assembly of ferritin dimers resulting in the formation of GQD-iron complex in the ferritin nanocages ((GQDs/Fe)AA). The (GQDs/Fe)AA shows high relaxivities in MRI and pH-sensitive fluorescence with strong fluorescence at low pH values and on MDA-MB-231 cells. As an imaging agent and a drug nanocarrier, (GQDs/Fe)AA exhibits negligible cytotoxicity on the cells and a high loading capacity (35%) of doxorubicin. Taken together, the (GQDs/Fe)AA shows promising applications in cancer diagnosis and therapy as a pH-responsive fluorophore, MRI agent, and drug nanocarrier.