A promising targeted gene delivery system: Folate-modified dexamethasone-conjugated solid lipid nanoparticles

Context: Non-viral gene delivery could deliver drugs/genes through cellular membranes and nuclear membranes by some modification of materials.

Objective: This study develops a kind of vector to target the cells through receptor-mediated pathways. Nuclear localization signal (NLS) was also used to increase the nuclear uptake of genetic materials.

Materials and methods: A lipid containing dexamethasone (Dexa) was synthesized as the material of the preparation of solid lipid nanoparticles (SLNs) and folate (Fa)-conjugated PEG-PE (Fa-PEG-PE) ligands were used to modify the SLNs. The in vitro cytotoxicity of the carriers at various concentrations (10, 20, 50, 100, and 200?μg/ml) were evaluated in KB human carcinoma cells (KB cells). In vivo transfection efficiency of the novel modified vectors was evaluated in disseminated peritoneal tumors on mice bearing KB cells.

Results: Fa-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) has a particle size of 258?nm, and the gene loading quantity of the vector was 90%. The in vitro cytotoxicity of Fa-PEG-PE-modified SLNs/pEGFP (Fa-SLNs/pEGFP) was low (cell viabilities were between 80% and 100% compared with controls). Fa-SLNs/pEGFP displayed remarkably higher transfection efficiency (40%) than non-modified SLNs/pEGFP (24%) and the vectors not containing Dexa (30%) in vivo.

Conclusion: The results demonstrate that Fa and Dexa could function as excellent active targeting ligands to improve the cell targeting and nuclear targeting ability of the carriers and the resulting vectors could be promising active targeting drug/gene delivery systems.