Lisen Lin1,2,3, Jibin Song1,2,3, Liang Song2, Kaimei Ke2, Yijing Liu1, Zijian Zhou1, Zheyu Shen1, Juan Li2, Zhèn Yáng1, Wei Tang1, Gang Niu1, Huanghao Yang2, Xiaoyuan Chen1
1Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892 USA
2MOE key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350108, China
3these authors contributed equally to this work
Tóm tắt
AbstractChemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical (.OH). There is a paucity of Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with .OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3−, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.
