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Liposomes or biological vesicles can be created from cholesterol, phospholipid, and water. Their stability is affected by their phospholipid composition which can influence disease treatment and drug delivery efficacy. In this study, the effect of phospholipid type on the formation and stability of liposomes using coarse-grained molecular dynamics simulations is investigated. For this purpose, the simulation study of the DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) and DPSM (Egg sphingomyelin) lipids were considered. All simulations were carried out using the Gromacs software and Martini force field 2.2. Energy minimization (3000 steps) model, equilibrium at constant volume to adjust the temperature at 400 Kelvin and equilibrium at constant pressure to adjust the pressure, at atmospheric pressure (1 bar) have been validated. Microsecond simulations, as well as formation analysis including density, radial distribution function, and solvent accessible surface area, demonstrated spherical nanodisc structures for the DPSM and DSPC liposomes. The results revealed that due to the cylindrical geometric structure and small-size head group, the DSPC lipid maintained its perfectly spherical structure. However, the DPSM lipid showed a conical geometric structure with larger head group than other lipids, which allows the liposome to form a micelle structure. Although the DSPC and DPSM lipids used in the laboratory tests exhibit liposome and micelle behaviors, the simulation results revealed their nanodisc structures. Energy analysis including overall energy, Van der Waals interaction energy, and electrostatic interaction energy showed that DPSM liposome is more stable than DSPC liposome.

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In the present research, we assumed that reducing the amounts of E6 and E7 oncoproteins by a specific siRNA sequence and recovering p53 and RB proteins, along with the recovery of the FOXO1 protein by applying anti-miR-182, would increase apoptosis and reduce proliferation rate in cancer cells. The HPV16-positive CaSki cervical cancer cell line was used. 48 hours after transfection of siRNA for targeting E6 and E7 oncoproteins and anti-miR-182, expression of its cellular targets p53, p21 and FOXO1 was assessed by real-time PCR, western blot analysis and immunocytofluorescence staining. In all treatments, apoptosis rate and viability were evaluated using Annexin-V-FITC apoptosis detection kits and MTT assays, respectively. Among the designed siRNAs, E6-1 and E7-2 proved the most effective in reducing E6 and E7 expressions by increasing the apoptotic rates to 12.4% and 16%, respectively, after 48 hours. Also, using anti-miR-182 increased apoptotic rate to 12.7% 48 hours after transfection of cervical cancer cells. The combinational use of either E6-1 or E7-2 siRNAs with anti-miR-182 resulted in a rise in apoptosis to 19.3% and 26%, respectively, higher than those obtained from the individual application of either without anti-miR-182. The simultaneous use of siRNA E6-1 and siRNA E7-2 with cisplatin increased sensitivity to cisplatin and reduced the viability of the cancer cells as compared to the use of cisplatin alone. The simultaneous use of cisplatin and anti-miR-182 had no considerable effect on viability or apoptosis rate compared to cisplatin alone.