title: Relationships between Poly(ethylene glycol) Modifications on RNA-Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time.
abstract: Two synthetic approaches that allow one to control PEG content within spherical nucleic acids (SNAs) have been developed. One approach begins with RNA-modified gold nanoparticles followed by a backfill of PEG 2K alkanethiols, and the other involves co-adsorption of the two entities on a gold nanoparticle template. These two methods have been used to explore the role of PEG density on the chemical and biological properties of RNA-SNAs. Such studies show that while increasing the extent of PEGylation within RNA-SNAs extends their blood circulation half-life in mice, it also results in decreased cellular uptake. Modified ELISA assays show that constructs, depending upon RNA and PEG content, have markedly different affinities for class A scavenger receptors, the entities responsible, in part, for cellular internalization of SNAs. In designing SNAs for therapeutic purposes, these competing factors must be considered and appropriately adjusted depending upon the desired use.
authors.affiliation: Department of Chemistry and International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Chinen
authors.affiliation: Department of Chemistry and International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Ferrer
authors.affiliation: Department of Chemistry and International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Merkel
authors.affiliation: Department of Chemistry and International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Mirkin
mesh_terms: D000327:Adsorption; D000818:Animals; D001692:Biological Transport; D006046:Gold / Q000737:chemistry; D006207:Half-Life; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011092:Polyethylene Glycols / Q000737:chemistry*; D012313:RNA / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011092:Polyethylene Glycols; D012313:RNA; D006046:Gold