Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide

Abstract

Epidermal growth factor receptor (EGFR) is a crucial protein that plays an important role in the maintenance and development of glioblastomas. The silencing or knockdown of EGFR is possible by administering a small interfering ribonucleic acid (siRNA). Lipid nanocapsules (LNCs) covered by chitosan were developed in our laboratory by a transacylation process. The resulting nanocapsules have a positive zeta potential that enables electrostatic interactions with the negatively-charged siRNA. Prior to transfection, the cytotoxicity of the nanocapsules by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) test was performed on the U87MG cell line to determine non-toxic levels of the LNCs to avoid cell mortality. Treatment of the U87MG cells with the chitosan-transacylated LNCs/anti-EGFR siRNA complex resulted in a reduction of EGFR expression by 51.95%±6.03% ( P ≤0.05) after 96 hours of incubation. It also increased the cellular sensitivity to temozolomide in comparison to untreated cells with siRNA. The largest increase in mortality was 62.55%±3.55% ( P <0.05). This successful knockdown provides proof for the concept of surface grafting of siRNA onto LNCs to modify cell sensitivity to temozolomide. The method could be implemented in future clinical models regarding the experimental treatment of glioblastoma cancer.

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

“…Additionally, NPs loaded with siRNAs targeting specific CSC genes [129][130][131] or with CSC inhibitory molecules [132][133][134][135][136] have been generated. To improve the specific targeting of CSCs, it might be worthwhile to create NPs loaded with both phytocompounds and non-phytochemical payloads.…”

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol

“…Aiming at providing an extensive overview on the immune impact of differently functionalized NCs, we report for the first time a comprehensive analysis on immune cell interaction with three different NCs coatings: pluronic F68 (Pluro), chitosan (Chito) and polyethylene glycol-polylactic acid (PEG-PLA, indicated in the text as PEG). Pluro, Chito and PEG coatings have been successfully used for NC functionalization for many applications 12 13 . PEG has been significantly employed to functionalize several nanomaterials to better deliver different genes and drugs such as camptothecin for the cancer treatment 14 15 16 17 .…”

“…Furthermore, very few results were reported about internalization of PEG coating into other immune cells subpopulations 20 . NCs loaded with chitosan have been extensively studied to enhance the therapeutic use of siRNAs 12 21 . Moreover, chitosan is commonly used as a transacylation polymer evidencing its non-toxicity 12 21 22 .…”

“…NCs loaded with chitosan have been extensively studied to enhance the therapeutic use of siRNAs 12 21 . Moreover, chitosan is commonly used as a transacylation polymer evidencing its non-toxicity 12 21 22 . In order to improve the NC drug delivery abilities, the NC shell can be also functionalized with pluronic, a nonionic triblock copolymer.…”

A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

“…The reaction produces alcohol as a secondary product, but it is easily eliminated by evaporation. Finally, the nanoparticles covered with chitosan by the new amide bond interactions are isolated and purified [72].…”