High mortality and rapid development of
metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery,
radiation therapy, and
chemotherapy, show less effectiveness in curbing the metastatic spread of
cancer cells and the formation of
metastases. A therapeutic platform, targeting the early stage of
metastasis cascade, could effectively prevent
metastasis dissemination. Herein, Fe/Mn-based
metal-organic frameworks (FMM) were constructed for the delivery of a specific
DNAzyme with high catalytic cleavage activity on the
metastasis-involved Twist
mRNA, thus efficiently inhibiting the invasion of
cancer cells through
DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic
therapy is achieved from the self-supplied
DNAzyme cofactors and efficient
glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist
DNAzyme with efficient gene therapy. Consequently, the effective elimination of
tumors and the blockage of
metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile
theranostic agents to combat metastatic
tumors.