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

Abstract

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 (Co3O4-DOX) for T1/T2 ratiometric magnetic resonance imaging (MRI)-monitored synergistic cancer therapy that simultaneously responds to intratumoral oxidability and acidity. Co3O4-DOX degraded under both H2O2-rich and acidic conditions, producing Co3+ and releasing DOX, not only resulted in an MRI contrast switch from T2 to T1, but also led to DOX luminescence recovery by weakening energy transfer. Thus, highly sensitive and selective H2O2 detection was achieved by these changes in MRI and luminescence signals. Importantly, Co3O4-DOX showed outstanding T1/T2 ratiometric MRI performance in vivo, significantly improving the contrast between tumor and normal tissues. Moreover, the produced Co3+ also resulted in intracellular radical generation for chemodynamic therapy, which had a synergistic effect with the photothermal and chemotherapy induced by Co3O4 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.