A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site.
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.
Tan
Mei Lin
ML
Department of Orthopaedics, St. Vincent's Hospital Melbourne, VIC, Australia.
Dunstan
Dave E
DE
Friedhuber
Anna M
AM
Choong
Peter F M
PF
Dass
Crispin R
CR
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
D004247:DNA; D048271:Chitosan