Methemoglobin as a redox-responsive nanocarrier to trigger the in situ anticancer ability of artemisinin

Learning from the antimalarial mechanism of artemisinin (ART) in nature, we explored methemoglobin (MHb) as a smart nanocarrier of ART, in which anticancer abilities can be turned on in situ through the upregulated reducing capacity of tumor tissue. Ultra violet–visible, electron paramagnetic resonance spectrometry and in vitro cell assessment proved that a reducing agent such as glutathione can work as an excellent biogenic trigger to reduce ferric iron in MHb to the ferrous state, activating the ability of ART to generate free radicals and resulting in cytotoxicity and apoptosis. In vivo investigations showed that the MHb–ART complex had encouraging anticancer outcomes. The bioinspired nanocarrier may pave a new way to achieve targeted toxicity to cancer cells with extremely low side effects.