Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 28, Pages 23693-23699Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b07889
Keywords
double-bundle DNA tetrahedron; antisense oligonucleotides; drug delivery; cancer therapy; self-assembly
Funding
- National Natural Science Foundations of China [21573051, 21708004, 31700871]
- National Basic Research Programs of China [2016YFA0201601, 2018YFA0208900]
- Science Fund for Creative Research Groups of the National Natural Science Foundation of China [21721002, 81421061]
- Beijing Municipal Science & Technology Commission [Z161100000116036]
- Key Research Program of Frontier Sciences, CAS [QYZDB-SSW-SLH029]
- K. C. Wong Education Foundation
- CAS Interdisciplinary Innovation Team
- Project of Biomedical Engineering Research Foundation of Shanghai Jiao Tong University [YG2016MS20]
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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.
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