چكيده لاتين
nowadays, gene transfer into cells through nano-carriers has gained attention as a powerful tool in the fields of medicine and biology. This approach has always faced challenges, including the inefficiency of existing nanostructures in the effective transfer of genes into cells. One of the efficient nano-carriers for gene delivery into cells is metal-organic frameworks (MOFs). This porous structure is composed of metal compounds and organic ligands, and it possesses unique features, including a complex three-dimensional structure, chemical stability, tunable pore sizes and channels, and molecular adsorption capability. In this study, to enhance the ability to transfer genes into various cell types, a hybrid nanostructure comprising zirconium fumarate metal-organic framework and polyethyleneimine polymer was utilized. The choice of zirconium fumarate metal-organic framework was due to its unique properties, including chemical stability, ability to deliver genes into cells, and lack of immune system stimulation. Initially, the mentioned nanostructure was synthesized using a solvothermal method. Subsequently, low molecular weight polyethyleneimine (2 KD) was modified with saponin and fluorine groups, and the final product was loaded onto the zirconium fumarate metal-organic framework through electrostatic interactions for the purpose of transferring a plasmid expressing fluorescent protein into human kidney embryonic cells. Not only did the resultant nanosystem show a high capability in transferring the plasmid expressing fluorescent protein, but it also demonstrated high efficiency in gene transfer at low plasmid concentrations and in the presence of 30% bovine fetal serum. The amount of plasmid transfer into the cells was evaluated using flow cytometry, with transfer rates reported as approximately 60%, 80%, and 40% in environments without bovine fetal serum, with low plasmid concentration, and with 30% bovine fetal serum, respectively. Furthermore, the mentioned nanoparticles were investigated for plasmid delivery to various cancer cell lines, including two human breast cancer cell lines (PC12 and MCF7), human colon cancer cells (HCT119), mouse embryonic fibroblasts (NIH3T3), and mouse neuronal cells (PC12). The highest transfection rate was observed in the PC12 cell line. Cytotoxicity testing on human kidney embryonic cells showed that the survival rate of these cells when exposed to the studied nanosystem was over 90%, indicating that this structure has lower toxicity compared to 25 KD polyethyleneimine and saponin- and fluorine-modified polyethyleneimine. Therefore, in this research, achieving a high efficiency in transferring the desired plasmid into the mentioned cells, the zirconium fumarate metal-organic framework modified with polyethyleneimine, saponin, and fluorine was introduced as a suitable non-viral carrier for efficient gene transfer due to its unique properties.
