Abstract

Magnetic hyperthermia therapy (MHT) and chemodynamic therapy (CDT) are non-invasive in situ treatments without depth limitations and with minimum adverse effects on surrounding healthy tissue. We herein report a mitochondria-targeting magnetothermogenic nanozyme ( [email protected] 2 O 4 NPs) for highly efficient cancer therapy. An iridium(III) complex ( Ir ) acts as a mitochondria-targeting agent on the surface of MnFe 2 O 4 NPs. On exposure to an alternating magnetic field (AMF), the [email protected] 2 O 4 NPs induce a localized increase in temperature causing mitochondrial damage (MHT effect). Meanwhile glutathione (GSH) reduces Fe(III) to Fe(II) on the NPs surface, which in turn catalyzes the conversion of H 2 O 2 to cytotoxic •OH (CDT effect). The depletion of GSH (a •OH scavenger) increases CDT efficacy, while the localized increase in temperature increases the rate of conversion of both Fe(III) to Fe(II) and H 2 O 2 to •OH further enhancing the CDT effect. In addition, the disruption of cellular redox homeostasis due to CDT, leads to greater sensitivity of the cell towards MHT. This nanoplatform integrates these excellent therapeutic properties, with two-photon microscopy (TPM) (demonstrated in vitro ) and magnetic resonance imaging (MRI) (demonstrated in vivo ) to enable the precise and effective treatment of cancer.