title: Improved antigen cross-presentation by polyethyleneimine-based nanoparticles.
abstract: OBJECTIVE
  In the development of therapeutic vaccines against cancer, it is important to design strategies for antigen cross-presentation to stimulate cell-mediated immune responses against tumor antigens.
  
  
  METHODS
  We developed a polyethyleneimine (PEI)-based protein antigen delivery system to promote cross-presentation through the major histocompatibility complex (MHC) I pathway using ovalbumin (OVA) as a model antigen. PEIs formed nanoparticles with OVA by electrostatic interactions, as demonstrated by electrophoresis analysis, scanning electron microscopy, and photon correlation spectroscopy analysis.
  
  
  RESULTS
  The nanoparticles were used to stimulate mouse bone marrow-derived dendritic cells in vitro and resulted in significantly more OVA(257-264)/MHC I complex presentation on dendritic cell surfaces. The activated dendritic cells interacted specifically with RF33.70 to stimulate interleukin-2 secretion. The cross-presentation promoting effect was more prominent in dendritic cells that had been cultured for longer periods of time (13 days). Further studies comparing the antigen presentation efficacies by other polyanionic agents, such as PLL or lysosomotropic agents, suggested that the unique "proton sponge effect" of PEI facilitated antigen escape from the endosome toward the MHC I pathway.
  
  
  CONCLUSIONS
  Such a PEI-based nanoparticle system may have the potential to be developed into an effective therapeutic vaccine delivery system.
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.forename: Yanzhu
authors.initials: Y
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.forename: Junhua
authors.initials: J
authors.lastname: Mai
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000643:Ammonium Chloride; D000818:Animals; D002478:Cells, Cultured; D002738:Chloroquine; D045142:Cross-Priming / Q000187:drug effects*; D003713:Dendritic Cells / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D005805:Genes, MHC Class I; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007376:Interleukin-2; C110366:OVA-8; D010446:Peptide Fragments; D000643:Ammonium Chloride; D002738:Chloroquine; D011094:Polyethyleneimine; D010047:Ovalbumin