Dual key co-activated nanoplatform for switchable MRI monitoring accurate ferroptosis-based synergistic therapy

Abstract

•Catalysis of CACN for ROS generation is “turned on” by co-activation of ATP and H+ •The accurate release of Dox can enhance the sensitivity of ferroptosis •ATP-triggered disassembly of CACN leads to high-sensitivity switchable MRI imaging •Switchable MRI can monitor ferroptosis-based therapy in combination with fluorescence Ferroptosis is of great significance for disease treatment and drug design because of its effective damage to drug-resistant cells. However, ferroptosis-based therapy presents challenges of low efficiency and low specificity, as well as the lack of reliable imaging technology for monitoring the therapeutic process. Herein, we have developed a tumor-microenvironment-tailored and co-activated catalytic nanoplatform (CACN) that was loaded with doxorubicin (Dox) molecules. Notably, the catalytic activity of CACN could be “turned on” for the specific ferroptosis treatment of cancer cells or tumors only upon co-activation by dual stimuli of ATP and slight acidity in the tumor microenvironment with the logic operation. Moreover, ATP-triggered disassembly of CACN led to the switchable MRI from negative to positive contrast, guaranteeing the sensitivity magnitude of MRI imaging. Furthermore, the switchable MRI signal is correlated with reactive oxygen species generation and Dox release, which is beneficial for monitoring the therapeutic process in combination with fluorescence imaging. Ferroptosis is of great significance for disease treatment and drug design because of its effective damage to drug-resistant cells. However, ferroptosis-based therapy presents challenges of low efficiency and low specificity, as well as the lack of reliable imaging technology for monitoring the therapeutic process. Herein, we have developed a tumor-microenvironment-tailored and co-activated catalytic nanoplatform (CACN) that was loaded with doxorubicin (Dox) molecules. Notably, the catalytic activity of CACN could be “turned on” for the specific ferroptosis treatment of cancer cells or tumors only upon co-activation by dual stimuli of ATP and slight acidity in the tumor microenvironment with the logic operation. Moreover, ATP-triggered disassembly of CACN led to the switchable MRI from negative to positive contrast, guaranteeing the sensitivity magnitude of MRI imaging. Furthermore, the switchable MRI signal is correlated with reactive oxygen species generation and Dox release, which is beneficial for monitoring the therapeutic process in combination with fluorescence imaging.