title: Controlling DNA-nanoparticle serum interactions.
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-1and 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.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9.|Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1.
authors.forename: Kyryl
authors.initials: K
authors.lastname: Zagorovsky
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9.
authors.forename: Leo Y T
authors.initials: LY
authors.lastname: Chou
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9; warren.chan@utoronto.ca.|Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1.|Department of Chemistry, University of Toronto, Toronto, ON, Canada M5S 3H6.|Department of Materials Science and Engineering, University of Toronto, Toronto, ON, Canada M5S 3E4.|Department of Chemical Engineering, University of Toronto, Toronto, ON, Canada M5S 3E5.
authors.forename: Warren C W
authors.initials: WC
authors.lastname: Chan
mesh_terms: D004247:DNA / Q000737:chemistry; D053837:DNA Cleavage; D003850:Deoxyribonuclease I / Q000032:analysis / Q000097:blood; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000706:statistics & numerical data; D049329:Nanostructures / Q000032:analysis / Q000627:therapeutic use; D009841:Oligonucleotides / Q000097:blood / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D044967:Serum
chemical_list: D009841:Oligonucleotides; D011092:Polyethylene Glycols; D004247:DNA; D003850:Deoxyribonuclease I
keywords: DNA nanostructures; controlled cargo release; nanoparticle assembly; serum resistance; serum stability