EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro

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.

COL3A1 and SNAP91: novel glioblastoma markers with diagnostic and prognostic value

“…Although the importance of numerous genes, including EGFR, bFGF, VEGF, IGF-1, p53 and p16 [14–19] to glioma progression has been well established. These genes are neither predictive of survival of glioma patients nor able to guide therapeutic decisions.…”

In Vivo Evaluation of Paclitaxel-Loaded Lipid Nanocapsules After Intravenous and Oral Administration on Resistant Tumor

“…LNCs can be prepared without the help of toxic organic solvent using a low-energy process that is suitable for scale-up and contain generally recognized as safe (GRAS) excipients, the formulation has been adapted to blood administration especially to avoid toxicity on blood cells [4]. LNCs are able to transport and protect drugs such as Ptx [5], etoposide [6], erlotinib [7], but also DNA [8] or siRNA [9]. Ptx-loaded LNCs (Ptx-LNCs) have shown a good toxicity profile, in fact Ptx maximum tolerated dose and LD50 were respectively multiplied by eight-and ten-fold for PtxLNCs in comparison to Taxol [10].…”

Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells

“…The obtained protein knockdown to 30% was also comparable to other cutting edge studies of similar brain targeting siRNA delivery vehicles. [41][42][43] However, while these systems have a positive charge, which may hamper their in vivo potential, the PCL of the LNP presented here ensures a net negative charge of the vehicle during systemic circulation.…”