title: Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides.
abstract: OBJECTIVE
  Cationized gelatin nanoparticles (GNPs) were used as carrier to improve delivery of immunostimulatory CpG oligonucleotides (CpG ODN) both in vitro and in vivo.
  
  
  METHODS
  Uptake of CpG ODN-loaded cationized gelatin nanoparticles (CpG-GNPs) into murine myeloid dendritic cells (DCs) and their respective immunostimulatory activity was monitored. In vivo, induction of cytokine secretion by CpG-GNPs was measured. For experiments on primary human cells, prototypes of the three CpG ODN classes were adsorbed onto GNPs. Uptake and induction of proinflammatory cytokines were assessed in human plasmacytoid DCs and B cells, the only existing human target cells for CpG ODN.
  
  
  RESULTS
  In the murine system, gelatin nanoparticle formulations enhanced the uptake and immunostimulatory activity of CpG ODN both in vitro and in vivo. Furthermore, delivery by cationized gelatin nanoparticles of CpG ODN of the classes B and C to primary human plasmacytoid DCs increased production of IFN-alpha, a key cytokine in the driving of both the innate and adaptive immune responses.
  
  
  CONCLUSIONS
  GNPs can be used as a biodegradable and well tolerated carrier to deliver CpG ODN to their target cells and strongly increase activation of the immune system. This concept may be applied as novel adjuvant for antiviral and antitumoral vaccines.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Butenandtstr. 5-13, 81377, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zwiorek
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
authors.forename: Julia
authors.initials: J
authors.lastname: Battiany
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.forename: Conrad
authors.initials: C
authors.lastname: Coester
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002412:Cations; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016898:Interferon-alpha / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051217:Toll-Like Receptor 9 / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D002412:Cations; D016207:Cytokines; D004337:Drug Carriers; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D005780:Gelatin