Simultaneously activating highly selective ratiometric MRI and synergistic therapy in response to intratumoral oxidability and acidity.

Low selectivity is a major problem for cancer theranostics that has promoted the development of molecularly-responsive nanomaterials. Herein, we report a novel doxorubicin (DOX)-loaded degradable cobalt oxide nanoprism (CoO-DOX) for T/T ratiometric magnetic resonance imaging (MRI)-monitored synergistic cancer therapy that simultaneously responds to intratumoral oxidability and acidity. CoO-DOX degraded under both HO-rich and acidic conditions, producing Co and releasing DOX, not only resulted in an MRI contrast switch from T to T, but also led to DOX luminescence recovery by weakening energy transfer. Thus, highly sensitive and selective HO detection was achieved by these changes in MRI and luminescence signals. Importantly, CoO-DOX showed outstanding T/T ratiometric MRI performance in vivo, significantly improving the contrast between tumor and normal tissues. Moreover, the produced Co also resulted in intracellular radical generation for chemodynamic therapy, which had a synergistic effect with the photothermal and chemotherapy induced by CoO and DOX, respectively. Under ratiometric MRI guidance, successful synergistic cancer therapy was performed on a tumor-bearing mice model. This work provides a new imaging application to improve selectivity that uses molecularly-responsive magnetic nanomaterials for ratiometric MRI tumor imaging and cancer theranostics.