A smart DNAzyme-MnO₂ nanosystem for efficient gene silencing.
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 (1)O2 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 10-23 DNAzyme for gene silencing. The release of Ce6 generates (1)O2 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.
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082 (China).
Huanhuan
H
Fan
Zilong
Z
Zhao
Guobei
G
Yan
Xiaobing
X
Zhang
Chao
C
Yang
Hongmin
H
Meng
Zhuo
Z
Chen
Hui
H
Liu
Weihong
W
Tan
D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D021881:DNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007477:Ions / Q000737:chemistry; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity; D010087:Oxides / Q000737:chemistry*; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
D002735:Chlorophyllides; C400152:DNA enzyme ED5; D021881:DNA, Catalytic; D004277:DNA, Single-Stranded; D007477:Ions; D017895:Manganese Compounds; D010087:Oxides; D011166:Porphyrins; D012333:RNA, Messenger; C402582:RNA-cleaving DNA 10-23; C062985:phytochlorin; C027424:manganese oxide; D005978:Glutathione
DNAzyme; gene silencing; manganese; nanotechnology; photodynamic therapy