title: The Impact of Protein Corona Formation on the Macrophage Cellular Uptake and Biodistribution of Spherical Nucleic Acids.
abstract: The effect of serum protein adsorption on the biological fate of Spherical Nucleic Acids (SNAs) is investigated. Through a proteomic analysis, it is shown that G-quadruplexes templated on the surface of a gold nanoparticle in the form of SNAs mediate the formation of a protein corona that is rich in complement proteins relative to SNAs composed of poly-thymine (poly-T) DNA. Cellular uptake studies show that complement receptors on macrophage cells recognize the SNA protein corona, facilitating their internalization, and causing G-rich SNAs to accumulate in the liver and spleen more than poly-T SNAs in vivo. These results support the conclusion that nucleic acid sequence and architecture can mediate nanoparticle-biomolecule interactions and alter their cellular uptake and biodistribution properties and illustrate that nucleic acid sequence is an important parameter in the design of SNA therapeutics.
authors.affiliation: International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.|Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Chinen
authors.affiliation: International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.|Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.
authors.forename: Chenxia M
authors.initials: CM
authors.lastname: Guan
authors.affiliation: International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.|Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Ko
authors.affiliation: International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.|Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.|Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Mirkin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis; D054856:G-Quadruplexes; D006801:Humans; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009696:Nucleic Acids / Q000378:metabolism*; D000066970:Protein Corona / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; D009696:Nucleic Acids; D000066970:Protein Corona; D011956:Receptors, Cell Surface
keywords: G-quadruplexes; Spherical Nucleic Acids; nanoparticle biodistribution; oligonucleotides; protein corona