title: Receptor-Mediated Entry of Pristine Octahedral DNA Nanocages in Mammalian Cells.
abstract: DNA offers excellent programming properties for the generation of nanometer-scaled polyhedral structures with a broad variety of potential applications. Translation to biomedical applications requires improving stability in biological fluids, efficient and selective cell binding, and/or internalization of the assembled DNA nanostructures. Here, we report an investigation on the selective mechanism of cellular uptake of pristine DNA nanocages in cells expressing the receptor "oxidized low-density lipoprotein receptor-1" (LOX-1), a scavenger receptor associated with cardiovascular diseases and, more recently, identified as a tumor marker. For this purpose a truncated octahedral DNA nanocage functionalized with a single biotin molecule, which allows DNA cage detection through the biotin-streptavidin assays, was constructed. The results indicate that DNA nanocages are stable in biological fluids, including human serum, and are selectively bound and very efficiently internalized in vesicles only in LOX-1-expressing cells. The amount of internalized cages is 30 times higher in LOX-1-expressing cells than in normal fibroblasts, indicating that the receptor-mediated uptake of pristine DNA nanocages can be pursued for a selective cellular internalization. These results open the route for a therapeutic use of pristine DNA cages targeting LOX-1-overexpressing tumor cells.
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata , Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vindigni
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata , Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Raniolo
authors.affiliation: Department of Biology, Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), University of Rome Tor Vergata , Via della Ricerca Scientifica 1, 00133, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Ottaviani
authors.affiliation: Department of Biology, Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), University of Rome Tor Vergata , Via della Ricerca Scientifica 1, 00133, Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Falconi
authors.forename: Oskar
authors.initials: O
authors.lastname: Franch
authors.forename: Birgitta R
authors.initials: BR
authors.lastname: Knudsen
authors.affiliation: Department of Biology, Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), University of Rome Tor Vergata , Via della Ricerca Scientifica 1, 00133, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata , Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Biocca
mesh_terms: D000818:Animals; D001692:Biological Transport; D004247:DNA; D006801:Humans; D008077:Lipoproteins, LDL; D049329:Nanostructures; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E; D004247:DNA
keywords: DNA nanocage stability; DNA nanotechnology; LOX-1; cell uptake; drug delivery; scavenger receptors