Multifunctional Graphene Oxide-based Triple Stimuli-Responsive Nanotheranostics

Construction of multifunctional stimuli-responsive nanosystems intelligently responsive to inner physiological and/or external irradiations based on nano-biotechnology can enable the on-demand drug release and improved diagnostic imaging to mitigate the side-effects of anticancer drugs and enhance the diagnostic/therapeutic outcome simultaneously. Here, a triple-functional stimuli-responsive nanosystem based on the co-integration of superparamagnetic Fe3O4 and paramagnetic MnOx nanoparticles (NPs) onto exfoliated graphene oxide (GO) nanosheets by a novel and efficient double redox strategy (DRS) is reported. Aromatic anticancer drug molecules can interact with GO nanosheets through supramolecular pi stacking to achieve high drug loading capacity and pH-responsive drug releasing performance. The integrated MnOx NPs can disintegrate in mild acidic and reduction environment to realize the highly efficient pH-responsive and reduction-triggered T-1-weighted magnetic resonance imaging (MRI). Superparamagnetic Fe3O4 NPs can not only function as the T-2-weighted contrast agents for MRI, but also response to the external magnetic field for magnetic hyperthermia against cancer. Importantly, the constructed biocompatible GO-based nanoplatform can inhibit the metastasis of cancer cells by downregulating the expression of metastasis-related proteins, and anticancer drug-loaded carrier can significantly reverse the multidrug resistance (MDR) of cancer cells.