Optimization of Superparamagnetic Iron Oxide Nanoparticles-Trimethyl Chitosan (SPION-TMC) as a siRNA Carrier to Inhibit HIV-1 nef

Despite the efficacy of current therapies against HIV-1 infection, these methods are not a permanent treatment because they cannot prevent the return of viremia from latent cell reservoirs. On the other hand, the virus may become resistant to these drugs. Therefore, providing safer and more effective therapeutic strategies, such as inhibition of genes by siRNA, is essential. The successful therapeutic application of siRNAs requires an efficient delivery system to target cells.

In this study, a specific siRNA was designed against the HIV-1 nef gene. Then a stable HEK293 cell line expressing HIV-1 nef was developed and after fabrication and evaluation of superparamagnetic iron oxide nanoparticles (SPION) coated with trimethyl chitosan, the efficiency of nanoparticles for delivering siRNA into the cells and inhibition of nef gene was investigated.

Iron oxide nanoparticles (spherical-shaped with an average size of 85nm and the average zeta potential of +29mV) were significantly effective in transporting siRNA into HEK293 cells compared to control groups and at the same time had low toxicity to the cells. In addition, SPION-TMC containing anti-nef siRNA inhibited about 85% of the expression of this gene in stable cells (compared to control cells).

The optimized SPION-TMC nanocarriers can be used as a promising approach in HIV-1 infection therapy. However, pre-clinical in vivo evaluation of the drug/siRNA delivery system efficiency remains to be conducted.