Novel cationic lipid that delivers siRNA and enhances therapeutic effect in lung cancer cells.

We have developed lipid-polycation-DNA (LPD) nanoparticles containing DOTAP and targeted with polyethylene glycol (PEG) tethered with anisamide (AA) to specifically deliver siRNA to H460 human lung carcinoma cells which express the sigma receptor. A novel non-glycerol based cationic lipid which contains both a guanidinium and a lysine residue as the cationic headgroup, i.e.

Covalent grafting of common trihydroxymethylaminomethane in the headgroup region imparts high serum compatibility and mouse lung transfection property to cationic amphiphile.

Clinical success of cationic transfection lipids in nonviral gene therapy continues to remain critically dependent on the use of serum compatible cationic amphiphiles efficient in delivering genes into our body cells. To this end, we demonstrate that covalent grafting of simple Tris-base component of the widely used biological Tris buffer in the headgroup region is capable of imparting high serum compatibility and intravenous mouse lung transfection properties to cationic amphiphile.

Dramatic influence of the orientation of linker between hydrophilic and hydrophobic lipid moiety in liposomal gene delivery.

A number of prior studies have demonstrated that the DNA-binding and gene transfection efficacies of cationic amphiphiles crucially depend on their various structural parameters including hydrophobic chain lengths, headgroup functionalities, and the nature of the linker-functionality used in tethering the polar headgroup and hydrophobic tails. However, to date addressing the issue of linker orientation remains unexplored in liposomal gene delivery. Toward probing the influence of linker orientation in cationic lipid mediated gene delivery, we have designed and synthesized two structurally isomeric remarkably similar cationic amphiphiles 1 and 2 bearing the same hydrophobic tails and the same polar headgroups connected by the same ester linker group.

Gene transfer efficacies of novel cationic amphiphiles with alanine, beta-alanine, and serine headgroups: a structure-activity investigation.

Herein, we report on the relative in vitro efficacies of nine novel non-glycerol based cationic amphiphiles with increasing hydrophobic tails and the amino acids serine, alanine and beta-alanine as the headgroup functionalities (lipids 1-9, Scheme 1) in transfecting multiple cultured cells including CHO, COS-1, MCF-7, and HepG2. The gene transfer efficiencies of lipids 1-9 were evaluated using the reporter gene assays in all the four cell lines and the whole cell histochemical X-gal staining assays in representative CHO cells. In CHO, HepG2, and MCF-7 cells, cationic lipids with alanine (4-6) and beta-alanine (7-9) headgroups were found to be remarkably more transfection efficient than their serine headgroup counterparts (1-3).

Common co-lipids, in synergy, impart high gene transfer properties to transfection-incompetent cationic lipids.

Efficacious cationic transfection lipids usually need either DOPE or cholesterol as co-lipid to deliver DNA inside the cell cytoplasm in non-viral gene delivery. If both of these co-lipids fail in imparting gene transfer properties, the cationic lipids are usually considered to be transfection inefficient. Herein, using both the reporter gene assay in CHO, COS-1 and HepG2 cells and the whole cell histochemical X-gal staining assay in representative CHO cells, we demonstrate that common co-lipids DOPE, Cholesterol and DOPC, when act in synergy, are capable of imparting improved gene transfer properties to a novel series of cationic lipids (1-5).

Design, syntheses, and transfection biology of novel non-cholesterol-based guanidinylated cationic lipids.

The design of efficacious cationic transfection lipids with guanidinium headgroups is an actively pursued area of research in nonviral gene delivery. Herein, we report on the design, syntheses, and gene transfection properties of six novel non-cholesterol-based cationic amphiphiles (1-6) with a single guanidinium headgroup in transfecting CHO, COS-1, MCF-7, A549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids 1-6 were evaluated using both the reporter gene and the whole cell histochemical X-gal staining assays.

Anchor-dependent lipofection with non-glycerol based cytofectins containing single 2-hydroxyethyl head groups.

Detailed structure-activity investigations aimed at probing the anchor chain length dependency for glycerol-based lipofectins have been reported previously. Herein, we report on the first detailed investigation on the anchor-dependent transfection biology of non-glycerol based simple monocationic cytofectins containing single 2-hydroxyethyl head group functionality using 11 new structural analogs of our previously published first generation of non-glycerol based transfection lipids (lipids 1-11). The C-14 and C-16 analogs of DOMHAC (lipids 4 and 5, respectively) were found to be remarkably efficient in transfecting COS-1 cells.