title: Efficient nucleic acid delivery to murine regulatory T cells by gold nanoparticle conjugates.
abstract: Immune responses have to be tightly controlled to guarantee maintenance of immunological tolerance and efficient clearance of pathogens and tumorigenic cells without induction of unspecific side effects. CD4(+) CD25(+) regulatory T cells (Tregs) play an important role in these processes due to their immunosuppressive function. Genetic modification of Tregs would be helpful to understand which molecules and pathways are involved in their function, but currently available methods are limited by time, costs or efficacy. Here, we made use of biofunctionalized gold nanoparticles as non-viral carriers to transport genetic information into murine Tregs. Confocal microscopy and transmission electron microscopy revealed an efficient uptake of the bioconjugates by Tregs. Most importantly, coupling eGFP-siRNA to those particles resulted in a dose and time dependent reduction of up to 50% of eGFP expression in Tregs isolated from Foxp3eGFP reporter mice. Thus, gold particles represent a suitable carrier for efficient import of nucleic acids into murine CD4(+) CD25(+) Tregs, superior to electroporation.
authors.affiliation: Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 7, 45141 Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gamrad
authors.affiliation: Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 7, 45141 Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rehbock
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 7, 45141 Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Barcikowski
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D018014:Gene Transfer Techniques; D006046:Gold / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009696:Nucleic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D015203:Reproducibility of Results; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D009696:Nucleic Acids; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D006046:Gold