Self-Assembled Double-Bundle DNA Tetrahedron for Efficient Antisense Delivery

被引:75
作者
Yang, Juanjuan [1 ]
Jiang, Qiao [2 ]
He, Lin [1 ]
Zhan, Pengfei [2 ]
Liu, Qing [2 ]
Liu, Shaoli [2 ]
Fu, Meifang [2 ]
Liu, Jianbing [2 ]
Li, Can [1 ]
Ding, Baoquan [2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, Bio X Inst, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200240, Peoples R China
[2] Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Nanosyst & Hierarch Fabricat, Beijing 100190, Peoples R China
[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
基金
中国国家自然科学基金;
关键词
double-bundle DNA tetrahedron; antisense oligonucleotides; drug delivery; cancer therapy; self-assembly; DRUG-RESISTANCE; OLIGONUCLEOTIDES; NANOSTRUCTURES; CELL; NANOPARTICLES; GENE; NANOTECHNOLOGY; INHIBITION; NANOCAGES; TRACKING;
D O I
10.1021/acsami.8b07889
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
DNA nanostructures are promising biomaterials capable of arranging multiple functional components with nanometer precision. Here, a double-bundle DNA tetrahedron is rationally designed to integrate with antisense oligonucleotides silencing proto-oncogene c-raf and nuclear targeting peptides. The functionalized DNA tetrahedron can be internalized by A549 cells and assists the delivery of antisense oligonucleotides toward the nucleus to increase the chance to downregulate target mRNA in nucleus and cytoplasm. Antisense strands released from the tetrahedron in response to the intracellular reducing environment can inhibit cell proliferation at a low concentration without transfection reagent. Finally, efficient knockdown of c-raf gene is observed, which verified our design. This designer DNA-based nanocarrier system will open a new avenue for efficient delivery of nucleic acid drugs.
引用
收藏
页码:23693 / 23699
页数:7
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