Efficient serum-resistant lipopolyplexes targeted to the folate receptor

In this work, we have developed and evaluated a new targeted lipopolyplex (LPP), by combining polyethylenimine (PEI), 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP)/Chol liposomes, the plasmids pCMVLuc/pCMVIL-12, and the ligand folic acid (FA), able to transfect HeLa and B16-F10 cells in the presence of very high concentration of serum (60% FBS). These complexes (Fol-LPP) have a net positive surface charge. The combination of folic acid with lipopolyplexes also enhanced significantly the transfection activity of the therapeutic gene interleukin-12 (IL-12), without any significant cytotoxicity. The specificity of the folate receptor (FR)-mediated gene transfer was corroborated by employing a folate receptor deficient cell line (HepG2). This formulation improved gene delivery showed by conventional lipoplexes or polyplexes resulting an efficient, simple, and nontoxic method for gene delivery of therapeutic genes in vitro and very probably in vivo.

Graphical abstractTransfection of HeLa cells by plain and Fol-lipopolyplexes, in the presence of 60% FBS. Complexes were formulated with linear PEI of 22 kDa (LPP22) with growing amounts of folic acid, at a lipid/DNA charge ratio (+/−) 5/1, containing 1 μg of pCMVIL-12 (*p < 0.01).Figure optionsDownload full-size imageDownload high-quality image (71 K)Download as PowerPoint slide