Abstract
Glioma are the most common malignant tumors of the central nervous system and remain associated with poor prognosis, despite the combination of chemotherapy and radiotherapy. EGFR targeting represents an interesting strategy to treat glioma. Indeed, a high level of endothelial growth factor receptors expression (EGFR), involved in the malignancy of the tumor, has been observed in glioma. Our strategy consisted in using EGFR siRNA entrapped into lipid nanocapsules (LNCs) via cationic liposomes. In vitro analyses on U87MG human glioma cells were performed to evaluate firstly the capacity of LNCs to efficiently deliver the siRNA and secondly the effect of EGFR siRNA targeting on U87MG proliferation. Then, the complement protein consumption was evaluated by CH50 assays to verify the suitability of the siRNA LNCs for systemic administration. The EGFR siRNA LNCs exhibited an adequate size lower than 150 nm as well as a neutral surface charge. The IC50 profile together with the 63% of protein extinction demonstrated the significant action of EGFR siRNA LNCs compared to scrambled LNCs. Dose and time-dependent survival assays showed a decrease of U87MG growth evaluated at 38%. Finally, low complement consumption demonstrated the suitability of EGFR siRNA LNCs for intravenous injection. In conclusion, EGFR siRNA LNCs demonstrated their capacity to efficiently encapsulate and deliver siRNA into U87MG human glioma cells, and will therefore be usable in the future for in vivo evaluation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 748-755 |
| Number of pages | 8 |
| Journal | International Journal of Pharmaceutics |
| Volume | 454 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2013 |
| Externally published | Yes |
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Keywords
- Brain tumor
- CH50
- Gene therapy
- Nanomedicine
- U87MG
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro. / Resnier, Pauline; David, Stephanie; Lautram, Nolwenn; Delcroix, Gaëtan J R; Clavreul, Anne; Benoit, Jean Pierre; Passirani, Catherine.
In: International Journal of Pharmaceutics, Vol. 454, No. 2, 2013, p. 748-755.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro
AU - Resnier, Pauline
AU - David, Stephanie
AU - Lautram, Nolwenn
AU - Delcroix, Gaëtan J R
AU - Clavreul, Anne
AU - Benoit, Jean Pierre
AU - Passirani, Catherine
PY - 2013
Y1 - 2013
N2 - Glioma are the most common malignant tumors of the central nervous system and remain associated with poor prognosis, despite the combination of chemotherapy and radiotherapy. EGFR targeting represents an interesting strategy to treat glioma. Indeed, a high level of endothelial growth factor receptors expression (EGFR), involved in the malignancy of the tumor, has been observed in glioma. Our strategy consisted in using EGFR siRNA entrapped into lipid nanocapsules (LNCs) via cationic liposomes. In vitro analyses on U87MG human glioma cells were performed to evaluate firstly the capacity of LNCs to efficiently deliver the siRNA and secondly the effect of EGFR siRNA targeting on U87MG proliferation. Then, the complement protein consumption was evaluated by CH50 assays to verify the suitability of the siRNA LNCs for systemic administration. The EGFR siRNA LNCs exhibited an adequate size lower than 150 nm as well as a neutral surface charge. The IC50 profile together with the 63% of protein extinction demonstrated the significant action of EGFR siRNA LNCs compared to scrambled LNCs. Dose and time-dependent survival assays showed a decrease of U87MG growth evaluated at 38%. Finally, low complement consumption demonstrated the suitability of EGFR siRNA LNCs for intravenous injection. In conclusion, EGFR siRNA LNCs demonstrated their capacity to efficiently encapsulate and deliver siRNA into U87MG human glioma cells, and will therefore be usable in the future for in vivo evaluation.
AB - Glioma are the most common malignant tumors of the central nervous system and remain associated with poor prognosis, despite the combination of chemotherapy and radiotherapy. EGFR targeting represents an interesting strategy to treat glioma. Indeed, a high level of endothelial growth factor receptors expression (EGFR), involved in the malignancy of the tumor, has been observed in glioma. Our strategy consisted in using EGFR siRNA entrapped into lipid nanocapsules (LNCs) via cationic liposomes. In vitro analyses on U87MG human glioma cells were performed to evaluate firstly the capacity of LNCs to efficiently deliver the siRNA and secondly the effect of EGFR siRNA targeting on U87MG proliferation. Then, the complement protein consumption was evaluated by CH50 assays to verify the suitability of the siRNA LNCs for systemic administration. The EGFR siRNA LNCs exhibited an adequate size lower than 150 nm as well as a neutral surface charge. The IC50 profile together with the 63% of protein extinction demonstrated the significant action of EGFR siRNA LNCs compared to scrambled LNCs. Dose and time-dependent survival assays showed a decrease of U87MG growth evaluated at 38%. Finally, low complement consumption demonstrated the suitability of EGFR siRNA LNCs for intravenous injection. In conclusion, EGFR siRNA LNCs demonstrated their capacity to efficiently encapsulate and deliver siRNA into U87MG human glioma cells, and will therefore be usable in the future for in vivo evaluation.
KW - Brain tumor
KW - CH50
KW - Gene therapy
KW - Nanomedicine
KW - U87MG
UR - http://www.scopus.com/inward/record.url?scp=84884156153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884156153&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2013.04.001
DO - 10.1016/j.ijpharm.2013.04.001
M3 - Article
VL - 454
SP - 748
EP - 755
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 2
ER -