PUBLICATION
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems
- Authors
- Berthault, N., Maury, B., Agrario, C., Herbette, A., Sun, J.S., Peyrieras, N., and Dutreix, M.
- ID
- ZDB-PUB-110803-29
- Date
- 2011
- Source
- Cancer Gene Therapy 18(10): 695-706 (Journal)
- Registered Authors
- Keywords
- siDNA, PEI, cholesterol, irradiation, antitumoral
- MeSH Terms
-
- Animals, Genetically Modified
- Mice
- Oligodeoxyribonucleotides*/analysis
- Oligodeoxyribonucleotides*/chemical synthesis
- Transfection
- Animals
- Female
- Neoplasms/genetics
- Neoplasms/mortality
- Neoplasms/therapy
- Genetic Vectors
- Kaplan-Meier Estimate
- Nanoparticles/administration & dosage
- Nanoparticles/chemistry*
- Nanoparticles/toxicity
- Cell Line, Transformed
- Xenograft Model Antitumor Assays
- Mice, Nude
- Zebrafish
- PubMed
- 21799529 Full text @ Cancer Gene Ther.
Citation
Berthault, N., Maury, B., Agrario, C., Herbette, A., Sun, J.S., Peyrieras, N., and Dutreix, M. (2011) Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems. Cancer Gene Therapy. 18(10):695-706.
Abstract
Introducing small DNA molecules (Dbait) impairs the repair of damaged chromosomes and provides a new method for enhancing the efficiency of radiotherapy in radio-resistant tumors. The radiosensitizing activity is dependent upon the efficient delivery of Dbait molecules into the tumor cells. Different strategies have been compared, to improve this key step. We developed a pipeline of assays to select the most efficient nanoparticles and administration protocols before preclinical assays: (i) molecular analyses of complexes formed with Dbait molecules, (ii) cellular tests for Dbait uptake and activity, (iii) live zebrafish embryo confocal microscopy monitoring for in vivo distribution and biological activity of the nanoparticles and (iv) tumor growth and survival measurement on mice with xenografted tumors. Two classes of nanoparticles were compared, polycationic polymers with linear or branched polyethylenimine (PEI) and covalently attached cholesterol (coDbait). The most efficient Dbait transfection was observed with linear PEI complexes, in vitro and in vivo. Doses of coDbait ten-fold higher than PEI/Dbait nanoparticles, and pretreatment with chloroquine, were required to obtain the same antitumoral effect on xenografted melanoma. However, with a 22-fold lower ‘efficacy dose/toxicity dose’ ratio as compared with Dbait/PEI, coDbait was selected for clinical trials.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping