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Simultaneous Fenton‐like Ion Delivery and Glutathione Depletion by MnO 2 ‐Based Nanoagent to Enhance Chemodynamic Therapy
Author(s) -
Lin LiSen,
Song Jibin,
Song Liang,
Ke Kaimei,
Liu Yijing,
Zhou Zijian,
Shen Zheyu,
Li Juan,
Yang Zhen,
Tang Wei,
Niu Gang,
Yang HuangHao,
Chen Xiaoyuan
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201712027
Subject(s) - glutathione , chemistry , hydroxyl radical , redox , glutathione disulfide , intracellular , mesoporous silica , radical , nanoparticle , biophysics , fenton reaction , nuclear chemistry , mesoporous material , inorganic chemistry , biochemistry , catalysis , materials science , nanotechnology , enzyme , biology
Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H 2 O 2 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 MnO 2 is reported that has both Fenton‐like Mn 2+ delivery and GSH depletion properties. In the presence of HCO 3 − , which is abundant in the physiological medium, Mn 2+ exerts Fenton‐like activity to generate . OH from H 2 O 2 . Upon uptake of MnO 2 ‐coated mesoporous silica nanoparticles (MS@MnO 2 NPs) by cancer cells, the MnO 2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn 2+ , resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO 2 , allows MS@MnO 2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.