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Enhanced Cisplatin Chemotherapy by Iron Oxide Nanocarrier-Mediated Generation of Highly Toxic Reactive Oxygen Species
Ping'an Ma1, Haihua Xiao2, Chang Yu1,3
1State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Abstract:
Reactive oxygen species (ROS) plays a key role in therapeutic effects as well as side effects of platinum drugs. Cisplatin mediates activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which triggers oxygen (O2) to superoxide radical (O2•-) and its downstream H2O2. Through the Fenton's reaction, H2O2 could be catalyzed by Fe2+/Fe3+ to the toxic hydroxyl radicals (•OH), which cause oxidative damages to lipids, proteins, and DNA. By taking the full advantage of Fenton's chemistry, we herein demonstrated tumor site-specific conversion of ROS generation induced by released cisplatin and Fe2+/Fe3+ from iron-oxide nanocarriers with cisplatin(IV) prodrugs for enhanced anticancer activity but minimized systemic toxicity.
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