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Lin, Li‐Sen; Song, Jibin; Song, Liang; Ke, Kaimei; Liu, Yijing; Zhou, Zijian; Shen, Zheyu; Li, Juan; Yang, Zhen; Tang, Wei; Niu, Gang; Yang, Huang‐Hao; Chen, Xiaoyuan
Angewandte Chemie International Edition, April 23, 2018, Volume: 57, Issue: 18Journal Article
Chemodynamic 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. Self‐reinforcing weapon: The Fenton‐like Mn2+ delivery and glutathione (GSH) depletion abilities of MnO2 allow it to exert enhanced chemodynamic efficacy in cancer treatment. An activatable theranostic platform based on multifunctional MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) has been developed for MRI‐monitored combination chemotherapy and chemodynamic therapy (CDT). ADS=antioxidant defense system.
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