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 °C were found to be best among th...

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Bibliographic Details
Published in:Journal of controlled release 2010-06, Vol.144 (2), p.196-202
Main Authors: Tan, Mei Lin, Dunstan, Dave E., Friedhuber, Anna M., Choong, Peter F.M., Dass, Crispin R.
Format: Article
Language:English
Subjects:
Animals
Antisense
Biological and medical sciences
Bone Neoplasms - therapy
Cancer
Chitosan
Chitosan - chemistry
DNA - chemistry
DNAzyme
General pharmacology
Humans
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticle
Nanoparticles - therapeutic use
Osteosarcoma - therapy
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Tumour
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Summary: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 °C were found to be best among the variables tested. Particles were 50–300 nm 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. Nanoencapsulated Dz13 with enhanced tumoricidal effect. Tumour cell changes from normal (left) to treated (right) include nuclear ( n) fragmentation, chromatin ( c) condensation, mitochondrial ( m) breakage, and plasma membrane ( p) blebbing. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2010.01.011