title: PEG-b-PPS-b-PEI micelles and PEG-b-PPS/PEG-b-PPS-b-PEI mixed micelles as non-viral vectors for plasmid DNA: tumor immunotoxicity in B16F10 melanoma.
abstract: Cationic micelles formed from poly(ethylene glycol)-bl-poly(propylene sulfide)-bl-poly(ethylene imine) (PEG-b-PPS-b-PEI) and from mixtures of poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-b-PPS) with PEG-b-PPS-b-PEI were explored as non-viral vectors for plasmid DNA (pDNA) transfection in a tumor immunotoxicity model. Complexes with pDNA were found to be templated exclusively by the size of the pDNA-free micelles and ranged from 240 nm (for PEG-b-PPS-b-PEI) to 30 nm (for mixed micelles of PEG-b-PPS/PEG-b-PPS-b-PEI). Both formulations transfected melanoma cells well in vitro. As a model with a functional read-out of tumor cell death, one with likely only small bystander effects, tumors were transfected with an antigen transgene, using an antigen to which the recipient animals had been previously vaccinated with a Th1-biasing adjuvant. Reduction in tumor growth, increase in intratumoral infiltration of cytotoxic T lymphocytes and accumulation of Th1-biasing cytokines indicated that both micelle formulations transfected efficiently compared with naked pDNA and with low cytotoxicity.
authors.affiliation: Institute of Bioengineering, Laboratory for Regenerative Medicine and Pharmacobiology, Station 15, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Diana
authors.initials: D
authors.lastname: Velluto
authors.forename: Susan N
authors.initials: SN
authors.lastname: Thomas
authors.forename: Eleonora
authors.initials: E
authors.lastname: Simeoni
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry*; D000922:Immunotoxins / Q000633:toxicity*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010957:Plasmids / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011095:Polyethylenes / Q000138:chemical synthesis / Q000737:chemistry*; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry*; D018675:Toxicity Tests; D014162:Transfection; D014780:Viruses / Q000187:drug effects
chemical_list: D000941:Antigens; D007097:Imines; D000922:Immunotoxins; D008823:Micelles; D011095:Polyethylenes; D013440:Sulfides; C569755:poly(ethylene glycol)-block-poly(propylene sulfide)-block-poly(ethylene imine); C515871:poly(ethylene glycol)-stabilized poly(propylene sulfide); C505405:poly(ethylene imine); D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA