title: The Sequence-Specific Cellular Uptake of Spherical Nucleic Acid Nanoparticle Conjugates.
abstract: The sequence-dependent cellular uptake of spherical nucleic acid nanoparticle conjugates (SNAs) is investigated. This process occurs by interaction with class A scavenger receptors (SR-A) and caveolae-mediated endocytosis. It is known that linear poly(guanine) (poly G) is a natural ligand for SR-A, and it has been proposed that interaction of poly G with SR-A is dependent on the formation of G-quadruplexes. Since G-rich oligonucleotides are known to interact strongly with SR-A, it is hypothesized that SNAs with higher G contents would be able to enter cells in larger amounts than SNAs composed of other nucleotides, and as such, cellular internalization of SNAs is measured as a function of constituent oligonucleotide sequence. Indeed, SNAs with enriched G content show the highest cellular uptake. Using this hypothesis, a small molecule (camptothecin) is chemically conjugated with SNAs to create drug-SNA conjugates and it is observed that poly G SNAs deliver the most camptothecin to cells and have the highest cytotoxicity in cancer cells. Our data elucidate important design considerations for enhancing the intracellular delivery of spherical nucleic acids.
authors.affiliation: Department of Biomedical Engineering, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Suguna P
authors.initials: SP
authors.lastname: Narayan
authors.affiliation: Department of Chemistry, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Chung Hang J
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Interdisciplinary Biological Sciences Program, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Chemistry, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Calabrese
authors.affiliation: Department of Materials Science and Engineering, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Auyeung
authors.affiliation: Department of Chemistry, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute for Complex Molecular Systems and Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600, MB, The Netherlands.
authors.forename: Olga J G M
authors.initials: OJ
authors.lastname: Goor
authors.affiliation: Department of Biomedical Engineering, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.|Department of Chemistry, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.|Department of Materials Science and Engineering, International Institute of Nanotechnology, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Mirkin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000493:pharmacokinetics; D004705:Endocytosis; D054856:G-Quadruplexes; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D058726:Nanoconjugates / Q000737:chemistry; D009696:Nucleic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D013379:Substrate Specificity
chemical_list: D004277:DNA, Single-Stranded; D058726:Nanoconjugates; D009696:Nucleic Acids; D006046:Gold
keywords: cellular uptake; guanine; nanoparticles; sequence-specific; spherical nucleic acids