title: Surface modified magnetic nanoparticles for immuno-gene therapy of murine mammary adenocarcinoma.
abstract: Cancer immuno-gene therapy is an introduction of nucleic acids encoding immunostimulatory proteins, such as cytokine interleukin 12 (IL-12), into somatic cells to stimulate an immune response against a tumor. Various methods can be used for the introduction of nucleic acids into cells; magnetofection involves binding of nucleic acids to magnetic nanoparticles with subsequent exposure to an external magnetic field. Here we show that surface modified superparamagnetic iron oxide nanoparticles (SPIONs) with a combination of polyacrylic acid (PAA) and polyethylenimine (PEI) (SPIONs-PAA-PEI) proved to be safe and effective for magnetofection of cells and tumors in mice. Magnetofection of cells with plasmid DNA encoding reporter gene using SPIONs-PAA-PEI was superior in transfection efficiency to commercially available SPIONs. Magnetofection of murine mammary adenocarcinoma with plasmid DNA encoding IL-12 using SPIONs-PAA-PEI resulted in significant antitumor effect and could be further refined for cancer immuno-gene therapy.
authors.affiliation: Kolektor Group, Nanotesla Institute, Ljubljana, Slovenia.
authors.forename: Sara
authors.initials: S
authors.lastname: Prijic
authors.forename: Lara
authors.initials: L
authors.lastname: Prosen
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
authors.forename: Janez
authors.initials: J
authors.lastname: Scancar
authors.forename: Rok
authors.initials: R
authors.lastname: Romih
authors.forename: Jaka
authors.initials: J
authors.lastname: Lavrencak
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Bregar
authors.forename: Andrej
authors.initials: A
authors.lastname: Coer
authors.forename: Mojca
authors.initials: M
authors.lastname: Krzan
authors.forename: Andrej
authors.initials: A
authors.lastname: Znidarsic
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
mesh_terms: D000180:Acrylic Resins / Q000633:toxicity; D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D015674:Mammary Neoplasms, Animal / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000633:toxicity; D013499:Surface Properties / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D014162:Transfection
chemical_list: D000180:Acrylic Resins; D058185:Magnetite Nanoparticles; D018664:Interleukin-12; C006903:carbopol 940; D011094:Polyethyleneimine; D004247:DNA