title: Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery.
abstract: Dendritic cells (DC) targeting vaccines require high efficiency for uptake, followed by DC activation and maturation. We used magnetic vectors comprising polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles, with hyaluronic acid (HA) of different molecular weights (<10 and 900 kDa) to reduce cytotoxicity and to facilitate endocytosis of particles into DCs via specific surface receptors. DNA encoding Plasmodium yoelii merozoite surface protein 1-19 and a plasmid encoding yellow fluorescent gene were added to the magnetic complexes with various % charge ratios of HA: PEI. The presence of magnetic fields significantly enhanced DC transfection and maturation. Vectors containing a high-molecular-weight HA with 100% charge ratio of HA: PEI yielded a better transfection efficiency than others. This phenomenon was attributed to their longer molecular chains and higher mucoadhesive properties aiding DNA condensation and stability. Insights gained should improve the design of more effective DNA vaccine delivery systems.
authors.affiliation: Department of Chemical Engineering, Monash University, Clayton, Victoria, Australia.
authors.forename: F M
authors.initials: FM
authors.lastname: Nawwab Al-Deen
authors.affiliation: Department of Chemical Engineering, Monash University, Clayton, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Selomulya
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Kong
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: S D
authors.initials: SD
authors.lastname: Xiang
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: R L
authors.initials: RL
authors.lastname: Coppel
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D003713:Dendritic Cells; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D005822:Genetic Vectors; D006820:Hyaluronic Acid / Q000494:pharmacology*; D060328:Magnetic Phenomena; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D010967:Plasmodium yoelii / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000953:Antigens, Protozoan; D005290:Ferric Compounds; D019444:Vaccines, DNA; C000499:ferric oxide; D011094:Polyethyleneimine; D006820:Hyaluronic Acid