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

详细信息    查看全文

• 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 (O<sub>2sub>) to superoxide radical (O<sub>2sub><sup>•sup><sup>–sup>) and its downstream H<sub>2sub>O<sub>2sub>. Through the Fenton’s reaction, H<sub>2sub>O<sub>2sub> could be catalyzed by Fe<sup>2+sup>/Fe<sup>3+sup> to the toxic hydroxyl radicals (<sup>•sup>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 Fe<sup>2+sup>/Fe<sup>3+sup> from iron-oxide nanocarriers with cisplatin(IV) prodrugs for enhanced anticancer activity but minimized systemic toxicity.