Related Experiment Video
Updated: Aug 13, 2026
Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery
Published on: April 16, 2019
In vivo potentialities of EWS-Fli-1 targeted antisense oligonucleotides-nanospheres complexes
Andrei Maksimenko1, Valerie Polard, Marie Villemeur
1Bioalliance Pharma SA, Paris 75015, France.
Abstract:
The EWS/FLI-1 fusion gene, resulting from a t(11;22) translocation, plays a key role in the pathogenesis of Ewing sarcoma. Previously, we have shown that antisense oligonucleotides designed against EWS-Fli-1 inhibited tumor growth in nude mice provided they were delivered intratumorally by nanocapsules or by CTAB-coated nanospheres. In this study, we have used two types of nanospheres (designated as type 1 and type 2 nanospheres) stabilized with chitosan for both intratumoral and systemic administration of oligonucleotides. Inhibition of the tumor growth in vivo was found to be dependent on the carrier type as well as on antisense oligonucleotide modification. Indeed, whereas both types of nanospheres were efficient in reducing tumor growth after intratumoral injection, we have obtained only with type 2 nanospheres an antitumoral effect after intravenous injection in a preliminary experiment. Additionally, the anticancer efficacy of a localized modification of the EWS-Fli-1 phosphodiester/phosphorothioate chimeric antisense oligonucleotide was demonstrated. In cell culture the oligonucleotides inhibit cell growth by their antisense activity. Further investigations are needed in vivo to learn the mechanism of action of the complexes.
Insights
Chitosan nanospheres effectively delivered EWS-FLI-1 antisense oligonucleotides to inhibit Ewing sarcoma growth. Type 2 nanospheres showed promise for systemic administration, warranting further in vivo investigation.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- The EWS/FLI-1 fusion gene is crucial in Ewing sarcoma pathogenesis.
- Previous studies demonstrated EWS-Fli-1 antisense oligonucleotides inhibit tumor growth via intratumoral delivery.
- Nanoparticle-based delivery systems are being explored for enhanced therapeutic efficacy.
Purpose of the Study:
- To evaluate chitosan-stabilized nanospheres for intratumoral and systemic delivery of EWS-Fli-1 antisense oligonucleotides.
- To assess the impact of nanosphere type and oligonucleotide modification on anticancer efficacy.
- To investigate the potential of nanocarriers for Ewing sarcoma treatment.
Main Methods:
- Two types of chitosan-stabilized nanospheres (type 1 and type 2) were used for oligonucleotide delivery.
- Intratumoral and intravenous administration routes were tested in vivo.
- Antisense oligonucleotide modifications were evaluated for their contribution to efficacy.
- In vitro cell growth inhibition assays were performed.
Main Results:
- Both nanosphere types effectively reduced tumor growth following intratumoral injection.
- Type 2 nanospheres demonstrated an antitumoral effect after intravenous administration in preliminary experiments.
- Oligonucleotide modification influenced anticancer efficacy.
- In cell culture, oligonucleotides inhibited cell growth via antisense activity.
Conclusions:
- Chitosan nanospheres are viable carriers for EWS-Fli-1 antisense oligonucleotides in Ewing sarcoma therapy.
- Type 2 nanospheres show potential for systemic delivery, offering a promising avenue for treatment.
- Further in vivo studies are required to elucidate the precise mechanisms of action for these nanocarrier complexes.
