Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo

Abstract

Cationic liposomes have been successfully used as an alternative approach to viral systems to deliver nucleic acids. However, high toxicity and inconsistent transfection efficiency have been associated with the currently available liposomes. Therefore, a novel cationic liposome was developed based on a synthetic cationic cardiolipin analogue (CCLA) to test the DNA transfection efficiency. This CCLA-based liposome was also used to determine the therapeutic efficacy of c-raf small interfering RNA (siRNA) in mice. In this report, we showed that the CCLA-based liposome was less toxic and effectively transfected reporter genes in vitro and in vivo. The transfection efficiency in mice was seven-fold higher than the commercially available DOTAP-based liposome. In addition, craf siRNA in the presence of CCLA-based liposome induced up to 62% of growth inhibition in cancer cells. Treatment of c-raf siRNA/CCLA complex in SCID mice bearing human breast xenograft tumors resulted in 73% of tumor growth suppression as compared to free c-raf siRNA group. In conclusion, a novel CCLA-based liposome showed less toxicity and broad usage both in vitro and in vivo with DNA and siRNA.

Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs

“…19,20 Attempts to improve delivery of siRNA in vivo include complexation of siRNA to polyethylenimine, formulation of siRNA with cationic lipids or collagen derivatives, and entrapment of siRNA in biodegradable microspheres. 19,[21][22][23][24][25] Most of these approaches aim primarily at improving the protection of siRNA from degradation and prolonging the circulation time. While this is indeed a crucial issue, efficient translocation of siRNA into the cytosol of the target cells is also of utmost importance.…”

ADAM‐12 (meltrin α) is involved in chondrocyte proliferation via cleavage of insulin‐like growth factor binding protein 5 in osteoarthritic cartilage

“…Similarly, chondrocytes were transfected with ADAM-12m siRNA in cationic cardiolipin analog-based liposome or nonsilencing siRNA in the liposome (29). These siRNA solutions were included in both upper gel and culture medium containing a mixture of TGF␤ and IGF-1, and then the inhibition rate was calculated by comparing the data from corresponding controls.…”

Functionalized non-viral cationic vectors for effective siRNA induced cancer therapy

“…Cullis et al [47] utilized this strategy to synthesize a novel dimer cationic lipid and achieved improved transfection activity as compared with a monomer lipid. Chien et al [48] adopted similar strategy to design novel cationic cardiolipin (dimeric cationic lipid) analogues. Cardiolipin has two negatively charged phosphate groups, which were replaced with quaternary ammonium groups termed CCLA.…”

“…To this view, Sangeeta Bhatia and co-workers [116] produced a library of 18 linear membrane-translocation domains that contained both polycationic peptide sequences [oligoarginines of varying net charge, TAT (48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60), and the HSV-1 tegument protein VP22] and amphipathic sequences (Penetratin (PEN) and Transportan (TP). Since lipid moieties such as myristoyl group are known to facilitate interactions with cell membranes [117], a myristoyl group (lipid portion) was added to the amino terminus to facilitate interactions with membrane lipids.…”