Enhanced Cisplatin Chemotherapy by Iron Oxide Nanocarrier-Mediated Generation of Highly Toxic Reactive Oxygen Species

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.