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 nanobiotechnology 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 MnO_x 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 π stacking to achieve high drug loading capacity and pH-responsive drug releasing performance. The integrated MnO_x NPs can disintegrate in mild acidic and reduction environment to realize the highly efficient pH-responsive and reduction-triggered T₁-weighted magnetic resonance imaging (MRI). Superparamagnetic Fe₃O₄ NPs can not only function as the T₂-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. A triple-functional biocompatible stimuli-responsive nanosystem based on the functionalized nanographene oxides is developed by a novel and efficient double redox strategy. This elaborately designed nanographene oxide-based nanoplatform exhibits the unique triple stimuli-responsivenesses for biomedical engineering, including pH-responsive drug release to inhibit the metastasis and reverse the multidrug resistance of cancer cells, pH-/redox-responsive magnetic resonance imaging and magnetic field-responsive hyperthermia of cancer.