Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

被引:64
作者
Jin, Yi [1 ]
Li, Zhenhua [1 ]
Liu, Huifang [1 ]
Chen, Shizhu [1 ]
Wang, Feng [1 ]
Wang, Ling [1 ]
Li, Nan [1 ]
Ge, Kun [1 ]
Yang, Xinjian [1 ]
Liang, Xing-Jie [2 ,3 ]
Zhang, Jinchao [1 ]
机构
[1] Hebei Univ, Key Lab Med Chem & Mol Diag, Minist Educ, Coll Chem & Environm Sci,Chem Biol Key Lab Hebei, 180 Wusidong Rd, Baoding 071002, Peoples R China
[2] Chinese Acad Sci, Ctr Excellence Nanosci, 11 ZhongGuanCun BeiYiTiao, Beijing 100190, Peoples R China
[3] Natl Ctr Nanosci & Technol, CAS Key Lab Biol Effects Nanomat & Nanosafety, 11 ZhongGuanCun BeiYiTiao, Beijing 100190, Peoples R China
基金
中国国家自然科学基金;
关键词
C VIRUS GENE; DNA NANOFLOWERS; DELIVERY; NANOPARTICLES; CELLS; DEOXYRIBOZYMES; MICROSPONGES; POLYCATIONS; CLEAVE; OXIDE;
D O I
10.1038/am.2017.34
中图分类号
T [工业技术];
学科分类号
08 ;
摘要
Safety and efficiency remain the critical hurdles hindering the practical application of gene agents, even though great effort has been made to develop various gene carriers. Herein, we present a novel biodegradable cancer therapeutic system based on DNA nanoflowers (DNFs) for targeted dual gene silencing. The therapeutic system was constructed by copying a rolling circle amplification template to produce long single-stranded DNAs with cell targeting and dual gene-silencing capability. The structure of the DNFs collapsed at acidic pH due to the decomposition of the co-assembled magnesium pyrophosphate, generating Mg2+ ions that act as cofactors for the DNAzymes and increase their ability to recognize and cleave target mRNAs. In vitro and in vivo studies demonstrated that the multifunctional DNFs showed promise for targeted cancer cell recognition, gene silencing, induction of apoptosis and inhibition of tumor growth. Considering the enhanced therapeutic effect and biocompatibility of this therapeutic platform, it is anticipated to be of great interest for the clinical treatment of cancers.
引用
收藏
页码:e365 / e365
页数:10
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