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Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides.
- Source :
-
ACS nano [ACS Nano] 2011 Nov 22; Vol. 5 (11), pp. 8783-9. Date of Electronic Publication: 2011 Oct 17. - Publication Year :
- 2011
-
Abstract
- Designed oligonucleotides can self-assemble into DNA nanostructures with well-defined structures and uniform sizes, which provide unprecedented opportunities for biosensing, molecular imaging, and drug delivery. In this work, we have developed functional, multivalent DNA nanostructures by appending unmethylated CpG motifs to three-dimensional DNA tetrahedra. These small-sized functional nanostructures are compact, mechanically stable, and noncytotoxic. We have demonstrated that DNA nanostructures are resistant to nuclease degradation and remain substantially intact in fetal bovine serum and in cells for at least several hours. Significantly, these functional nanostructures can noninvasively and efficiently enter macrophage-like RAW264.7 cells without the aid of transfection agents. After they are uptaken by cells, CpG motifs are recognized by the Toll-like receptor 9 (TLR9) that activates downstream pathways to induce immunostimulatory effects, producing high-level secretion of various pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12. We also show that multivalent CpG motifs greatly enhance the immunostimulatory effect of the nanostructures. Given the high efficacy of these functional nanostructures and their noncytotoxic nature, we expect that DNA nanostructures will become a promising tool for targeted drug delivery.<br /> (© 2011 American Chemical Society)
- Subjects :
- Adjuvants, Immunologic genetics
Adjuvants, Immunologic metabolism
Animals
Biological Transport
Cell Line
Cell Survival drug effects
DNA toxicity
Drug Carriers toxicity
Mice
CpG Islands
DNA chemistry
Drug Carriers chemistry
Intracellular Space metabolism
Nanostructures chemistry
Oligonucleotides genetics
Oligonucleotides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 5
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 21988181
- Full Text :
- https://doi.org/10.1021/nn202774x