title: A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site.
abstract: We demonstrate that Dz13, a DNA enzyme that cleaves c-Jun mRNA, and is capable of inhibiting cancer cell growth in vitro, can be encapsulated into chitosan nanoparticles. For optimisation of this chitosan-based formulation, pH 6, 0.02% chitosan concentration, and 55 degrees C were found to be best among the variables tested. Particles were 50-300nm in diameter and encapsulated Dz13 was active when particles were exposed to cancer cells. Nanoparticles were stable during storage even for a month, but were not stable in mouse and human serum. In two different clinically-relevant disease models, and using a clinically-adoptable dosing regimen, these Dz13-nanoparticles were shown to be efficacious against a bone tumour (osteosarcoma), for which no real cure exists currently. However, no toxicity against other bone-dwelling cells was observed with the formulation, and no side-effects were noted in vivo in lymphatic and reticuloendothelial tissues proximal and distal to the administration site.
authors.affiliation: Department of Orthopaedics, St. Vincent's Hospital Melbourne, VIC, Australia.
authors.forename: Mei Lin
authors.initials: ML
authors.lastname: Tan
authors.forename: Dave E
authors.initials: DE
authors.lastname: Dunstan
authors.forename: Anna M
authors.initials: AM
authors.lastname: Friedhuber
authors.forename: Peter F M
authors.initials: PF
authors.lastname: Choong
authors.forename: Crispin R
authors.initials: CR
authors.lastname: Dass
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000628:therapy; D048271:Chitosan / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000628:therapy
chemical_list: D004247:DNA; D048271:Chitosan