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siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibition in vivo
A L Ramon1, J R Bertrand, H de Martimprey
1CNRS UMR 8203 Vectorologie et thérapeutiques anticancéreuses, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.
Abstract:
Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles.
Insights
Targeted nanoparticles effectively delivered small interfering RNA (siRNA) to Ewing's sarcoma tumors by targeting the CD99 glycoprotein. This approach significantly improved gene silencing compared to non-targeted nanoparticles.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Ewing's sarcoma is a rare pediatric bone cancer driven by the EWS/Fli-1 abnormality.
- Nanoparticle-mediated delivery of small interfering RNA (siRNA) shows promise for inhibiting tumor growth.
- CD99, a cell membrane glycoprotein, is overexpressed in Ewing's sarcoma cells.
Purpose of the Study:
- To design CD99-targeted nanoparticles for enhanced siRNA delivery to Ewing's sarcoma cells.
- To improve the specificity and efficacy of siRNA therapy for Ewing's sarcoma.
- To utilize biotinylated poly(isobutylcyanoacrylate) nanoparticles and biotin-streptavidin coupling for targeted delivery.
Main Methods:
- Development of biotinylated nanoparticles as a platform for targeted ligand attachment.
- Utilizing the biotin-streptavidin system to conjugate ligands targeting CD99.
- In vivo validation of targeted nanoparticle-mediated siRNA delivery in a murine Ewing's sarcoma model.
Main Results:
- CD99-targeted nanoparticles successfully delivered siRNA in vivo.
- Targeted nanoparticles achieved 78% ± 6% inhibition of the Ewing's sarcoma-related gene expression.
- Non-targeted nanoparticles resulted in only 41% ± 9% gene expression inhibition.
Conclusions:
- CD99-targeted nanoparticles represent an effective strategy for specific siRNA delivery in Ewing's sarcoma.
- This targeted approach significantly enhances the therapeutic efficacy of siRNA compared to non-targeted methods.
- Nanoparticle-based drug delivery holds potential for improving pediatric cancer treatments.
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