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

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• 作者：Ping’an Ma ; Haihua Xiao ; Chang Yu ; Jianhua Liu ; Ziyong Cheng ; Haiqin Song ; Xinyang Zhang ; Chunxia Li ; Jinqiang Wang ; Zhen GuJun Lin
• 刊名：Nano Letters
• 出版年：2017
• 出版时间：February 8, 2017
• 年：2017
• 卷：17
• 期：2
• 页码：928-937
• 全文大小：786K
• ISSN：1530-6992

文摘

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.