title: DNA nanotubes as intracellular delivery vehicles in vivo.
abstract: DNA-based nanoconstructs possess great potential for biomedical applications. However, the in vivo behavior of such constructs at the microscopic tissue/cell level as well as their inflammatory potential is largely unknown. Unmethylated CpG sequences of DNA are recognized by Toll-like receptor 9 (TLR9), and thus initiate an innate immune response. In this study, we investigated the use of DNA-based nanotubes as carrier systems for CpG delivery and their effect on immune cells in vivo and in real time. DNA nanotubes were microinjected into skeletal muscle of anesthetized mice. Using in vivo microscopy, we observed that the DNA tubes were internalized within minutes by tissue-resident macrophages and localized in their endosomes. Only microinjection of CpG-decorated DNA nanotubes but not of plain DNA nanotubes or CpG oligonucleotides induced a significant recruitment of leukocytes into the muscle tissue as well as activation of the NF-ĸB pathway in surrounding cells. These results suggest that DNA nanotubes are promising delivery vehicles to target tissue macrophages, whereupon the immunogenic potential depends on the decoration with CpG oligonucleotides.
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Sellner
authors.affiliation: Department of Physics & Center for NanoScience, Ludwig-Maximilians-Universität München, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.
authors.forename: Samet
authors.initials: S
authors.lastname: Kocabey
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Nekolla
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
authors.affiliation: Department of Physics & Center for NanoScience, Ludwig-Maximilians-Universität München, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Liedl
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 Munich, Germany. Electronic address: markus.rehberg@lrz.uni-muenchen.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Rehberg
mesh_terms: D000818:Animals; D002460:Cell Line; D018899:CpG Islands; D004247:DNA / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D043942:Nanotubes; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D004337:Drug Carriers; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA
keywords: CpG; DNA nanotechnology; Delivery; Macrophage; Self assembly; Single stranded tile