title: Enhancement of dendritic cells transfection in vivo and of vaccination against B16F10 melanoma with mannosylated histidylated lipopolyplexes loaded with tumor antigen messenger RNA.
abstract: We report the preparation of mannosylated nanoparticles loaded with messenger RNA (mRNA) that enhance the transfection of dendritic cells (DCs) in vivo and the anti-B16F10 melanoma vaccination in mice. Mannosylated and histidylated lipopolyplexes (Man(11)-LPR100) were obtained by adding mannosylated and histidylated liposomes to mRNA-PEGylated histidylated polylysine polyplexes. Upon intravenous injection, ∼9% of the radioactivity of technetium 99 m-labeled lipopolyplexes measured in the liver, spleen, lungs, and kidneys was found in the spleen. We demonstrate that spleen from mice injected with enhanced green fluorescent protein (EGFP) mRNA-loaded Man(11)-LPR100 contained four times more DCs expressing EGFP than that from mice injected with sugar-free LPR100. This better transfection of DCs is correlated with a better inhibition of B16F10 melanoma growth and an increased survival time when mice were immunized with MART-1 mRNA-loaded Man(11)-LPR100. These results indicate that mannosylated and histidylated LPR is an efficient system for the delivery of tumor antigen mRNA in splenic DCs aiming to induce an anticancer immune response.
  
  
  BACKGROUND
  This paper discusses the preparation of mannosylated nanoparticles loaded with messenger RNA that enhance the transfection of dendritic cells (DCs) in vivo and the anti-B16F10 melanoma vaccination in mice. The authors describe an efficient system for the delivery of tumor antigen mRNA in splenic DCs aiming to induce an anticancer immune response.
authors.affiliation: Centre de Biophysique Moléculaire CNRS UPR 4301, University and Inserm, Orléans, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Perche
authors.forename: Thierry
authors.initials: T
authors.lastname: Benvegnu
authors.forename: Mathieu
authors.initials: M
authors.lastname: Berchel
authors.forename: Loic
authors.initials: L
authors.lastname: Lebegue
authors.forename: Chantal
authors.initials: C
authors.lastname: Pichon
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffrès
authors.forename: Patrick
authors.initials: P
authors.lastname: Midoux
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D008297:Male; D008358:Mannose / Q000737:chemistry; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D012333:RNA, Messenger / Q000737:chemistry / Q000276:immunology*; D014162:Transfection / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012333:RNA, Messenger; D006639:Histidine; D008358:Mannose