A Smart DNAzyme-MnO2 Nanosystem for Efficient Gene Silencing

被引:301
作者
Fan, Huanhuan [1 ]
Zhao, Zilong [1 ]
Yan, Guobei [1 ]
Zhang, Xiaobing [1 ]
Yang, Chao [1 ]
Meng, Hongmin [1 ]
Chen, Zhuo [1 ]
Liu, Hui [1 ]
Tan, Weihong [1 ]
机构
[1] Hunan Univ, Innovat Ctr Chem & Mol Med,Mol Sci & Biomed Lab, State Key Lab Chemo Biosensing & Chemometr, Coll Chem & Chem Engn,Coll Biol Collaborat, Changsha 410082, Hunan, Peoples R China
关键词
DNAzyme; gene silencing; manganese; nanotechnology; photodynamic therapy; MNO2; NANOSHEET; LEAD; SENSOR; PROBE; SITE; ION;
D O I
10.1002/anie.201411417
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
DNAzymes hold promise for gene-silencing therapy, but the lack of sufficient cofactors in the cell cytoplasm, poor membrane permeability, and poor biostability have limited the use of DNAzymes in therapeutics. We report a DNAzyme-MnO2 nanosystem for gene-silencing therapy. MnO2 nanosheets adsorb chlorin e6-labelled DNAzymes (Ce6), protect them from enzymatic digestion, and efficiently deliver them into cells. The nanosystem can also inhibit O-1(2) generation by Ce6 in the circulatory system. In the presence of intracellular glutathione (GSH), MnO2 is reduced to Mn(2+)ions, which serve as cofactors of 10-23DNAzyme for gene silencing. The release of Ce6 generates O-1(2) for more efficient photodynamic therapy. The Mn(2+)ions also enhance magnetic resonance contrast, providing GSH-activated magnetic resonance imaging (MRI) of tumor cells. The integration of fluorescence recovery and MRI activation provides fluorescence/MRI bimodality for monitoring the delivery of DNAzymes.
引用
收藏
页码:4801 / 4805
页数:5
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