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A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site

Tan, Mei Lin and Dunstan, David E and Friedhuber, Anna M and Choong, Peter F. M and Dass, Crispin R (2010) A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site. Journal of Controlled Release, 144 (2). pp. 196-202. ISSN 0168-3659

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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 °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.

Item Type: Article
Uncontrolled Keywords: ResPubID21861, nanoparticle, DNAzyme, antisense, chitosan, cancer, tumour
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1112 Oncology and Carcinogenesis
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Depositing User: VUIR
Date Deposited: 21 Jun 2012 06:42
Last Modified: 08 Feb 2015 23:12
URI: http://vuir.vu.edu.au/id/eprint/7566
DOI: 10.1016/j.jconrel.2010.01.011
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Citations in Scopus: 7 - View on Scopus

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