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

Autor: S. Ben Djemaa, Emilie Allard-Vannier, S. Eljack, Hervé Marchais, Nicolas Aubrey, Katel Hervé-Aubert, Zineb Lakhrif, J. Bruniaux, Stephanie David, Igor Chourpa
Přispěvatelé: Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours (UT), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Institut National du Cancer (INCa), France, Institut National du Cancer (INCA) France, Fondation ARC, France, Ligue Nationale Contre le Cancer (LNCC), France [ARC_INCa_LNCC_7636], 'Region Centre-Val de Loire' (NCIS Project), France, 'Canceropole Grand Ouest', France, French Higher Education and Research ministry under the program 'Investissements d'avenir'French National Research Agency (ANR) [LabEx MAbImprove ANR-10-LABX-53-01], Université de Tours, Institut National de la Recherche Agronomique (INRA)-Université de Tours
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Small interfering RNA
animal structures
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Receptor
ErbB-2
media_common.quotation_subject
small interfering rna (sirna)
Green Fluorescent Proteins
Pharmaceutical Science
scfv anti-her2
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
02 engineering and technology
survivin
030226 pharmacology & pharmacy
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Line
Tumor
Survivin
medicine
Humans
RNA
Small Interfering
Internalization
skin and connective tissue diseases
media_common
Chemistry
Magnetic Phenomena
Cancer
021001 nanoscience & nanotechnology
medicine.disease
superparamagnetic iron oxide nanoparticles (spion)
Coculture Techniques
3. Good health
Cell culture
Cancer research
Nanoparticles
Breast cancer cells
Nanocarriers
0210 nano-technology
Single-Chain Antibodies
Zdroj: International Journal of Pharmaceutics
International Journal of Pharmaceutics, Elsevier, 2019, 569, 5 p. ⟨10.1016/j.ijpharm.2019.118572⟩
5. Annual Meeting of the French-Society-of-Nanomedicine on Nanomedicine (SFNano)-from particule design to applications
5. Annual Meeting of the French-Society-of-Nanomedicine on Nanomedicine (SFNano)-from particule design to applications, Dec 2018, Montpellier, France
ISSN: 0378-5173
DOI: 10.1016/j.ijpharm.2019.118572⟩
Popis: Section spéciale du Meeting SFNano 2018 : Nanomedicine- from particle design to applications (2018/12/03_2018/12/05, Montpellier, FRA), edited by Nathalie Mignet, Chantal Pichon et Marie-Pierre Rols; International audience; 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.
Databáze: OpenAIRE
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