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

被引：590
|
作者：
Ma, Ping'an [1 ]
Xiao, Haihua [2 ]
Yu, Chang [1 ,3 ]
Liu, Jianhua [4 ,5 ]
Cheng, Ziyong [1 ]
Song, Haiqin [1 ]
Zhang, Xinyang [1 ]
Li, Chunxia [1 ]
Wang, Jinqiang [6 ,7 ]
Gu, Zhen [6 ,7 ]
Lin, Jun [1 ]
机构：
[1] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Rare Earth Resource Utilizat, Changchun 130022, Peoples R China
[2] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China
[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[4] Jilin Univ, Hosp 2, Dept Radiol, Changchun 130041, Peoples R China
[5] Jilin Univ, Coll Chem, State Key Lab Inorgan Synth & Preparat Chem, Changchun 130012, Peoples R China
[6] Univ N Carolina, Joint Dept Biomed Engn, Chapel Hill, NC USA
[7] North Carolina State Univ, Raleigh, NC 27695 USA
来源：
NANO LETTERS | 2017年 / 17卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Drug delivery; cisplatin; iron oxide; Fenton's reaction; reactive oxygen species; MOTEXAFIN GADOLINIUM; DELIVERY; DRUG; PRODRUG; MECHANISMS; RESISTANCE; NANOPARTICLES; INFLAMMATION; ARTEMISININS; OTOTOXICITY;
D O I：
10.1021/acs.nanolett.6b04269
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
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 dinudeotide phosphate (NADPH) oxidase (NOX), which triggers oxygen (O-2) to superoxide radical (O-2(center dot-)) and its downstream H2O2. Through the Fenton's reaction, H2O2 could be catalyzed by Fe2+/Fe3+ to the toxic hydroxyl radicals ((OH)-O-center dot), 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.
引用
收藏
页码：928 / 937
页数：10
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