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Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13600-13605. Epub 2016 Nov 16.

Controlling DNA-nanoparticle serum interactions.

Zagorovsky K1,2, Chou LY1, Chan WC3,2,4,5,6.

Author information

1
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9.
2
Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1.
3
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9; warren.chan@utoronto.ca.
4
Department of Chemistry, University of Toronto, Toronto, ON, Canada M5S 3H6.
5
Department of Materials Science and Engineering, University of Toronto, Toronto, ON, Canada M5S 3E4.
6
Department of Chemical Engineering, University of Toronto, Toronto, ON, Canada M5S 3E5.

Abstract

Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h-1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.

KEYWORDS:

DNA nanostructures; controlled cargo release; nanoparticle assembly; serum resistance; serum stability

PMID:
27856755
PMCID:
PMC5137734
DOI:
10.1073/pnas.1610028113
[Indexed for MEDLINE]
Free PMC Article

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