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.