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Communication Dans Un Congrès Année : 2018

Magnetic nanocarriers for the specific delivery of siRNA: Contribution of breast cancer cells active targeting for down-regulation efficiency

J. Bruniaux
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Nicolas Aubrey
S. Eljack
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H. Marchais
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Katel Hervé-Aubert
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Igor Chourpa
S. David
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Résumé

The association between superparamagnetic iron oxide nanoparticles (SPION), carrying small interfering RNA (siRNA) as therapeutic agents and humanized anti- human epidermal growth factor receptor-2 (HER2) single-chain antibody fragments (scFv) for the active delivery into HER2-overexpressing cells appears as an interesting approach for patients with HER2-overexpressing advanced breast cancer. The obtained Targeted Stealth Magnetic siRNA Nanovectors (TS-MSN) are formulated by combining: (i) the synthesis protocol of Targeted Stealth Fluorescent Particles (T-SFP) which form the core of TS-MSN and (ii) the formulation protocol allowing the loading of T-SFP with polyplexes (siRNA and cationic polymers). TS-MSN have suitable physico-chemical characteristics for intravenous administration and protect siRNA against enzymatic degradation up to 24 h. The presence of HER2-targeting scFv on TS-MSN allowed an improved internalization (3-4 times more compared to untargeted S-MSN) in HER2-overexpressing breast cancer cells (BT-474). Furthermore, anti-survivin siRNA delivered by TS-MSN in HER2-negative breast-cancer control cells (MDA-MB-231) allowed significant down-regulation of the targeted anti-apoptotic protein of about 70%. This protein down-regulation increased in HER2 + cells to about 90% (compared to 70% with S-MSN in both cell lines) indicating the contribution of the HER2-active targeting. In conclusion, TS-MSN are promising nanocarriers for the specific and efficient delivery of siRNA to HER2-overexpressing breast cancer cells.
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Dates et versions

hal-02737799 , version 1 (02-06-2020)

Identifiants

  • HAL Id : hal-02737799 , version 1
  • PRODINRA : 489932

Citer

J. Bruniaux, E. Allard-Vannier, Nicolas Aubrey, Z. Lakhrif, S. Ben Djemaa, et al.. Magnetic nanocarriers for the specific delivery of siRNA: Contribution of breast cancer cells active targeting for down-regulation efficiency. 5. Annual Meeting of the French-Society-of-Nanomedicine on Nanomedicine (SFNano) - from particule design to applications, Dec 2018, Montpellier, France. ⟨hal-02737799⟩
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