Effects of spacers within a series of novel folate-containing lipoconjugates on the targeted delivery of nucleic acids

Folate-Equipped Cationic Liposomes Deliver Anti-MDR1-siRNA to the Tumor and Increase the Efficiency of Chemotherapy

“…We have recently shown that cationic liposome F consisting of the cholesterol-based polycationic amphiphile 2X3 (32.7 molar %), the zwitterionic helper lipid DOPE (65. [2,32,34]. In this study, we performed a detailed analysis of acute and chronic toxicity of this liposomal formulation in healthy mice, examined the correlation between the abundance of FR on the cell surface and intratumoral accumulation of NA mediated by liposome F, and analyzed the antitumor effect of PCHT supported by anti-MDR1 siRNA delivered by liposome F on a multidrug-resistant KB-8-5 tumor xenograft in SCID mice.…”

“…The cationic lipid 2X3 and the folate lipoconjugate O -{2-[ rac -2,3-di(tetradecyloxy)prop-1-yloxycarbonyl]aminoethyl}- O’ -[2-(pteroyl-L-glutam-5-yl)aminoethyl]octadecaethyleneglycol (FC) were synthesized as we have described previously [ 2 , 30 , 32 ]. Briefly, 1,2-di- O -ditetradecyl- rac -glycerol was activated with 4-nitrophenyl chloroformate and treated with PEG diamine.…”

“…were synthesized as we have described previously [2,30,32]. Briefly, 1,2-di-O-ditetradecyl-rac-glycerol was activated with 4-nitrophenyl chloroformate and treated with PEG diamine.…”

“…We previously developed an effective liposomal NA delivery system based on the polycationic amphiphile 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride (2X3) and the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoetha-nolamine (DOPE) [2,30,31], which effectively delivers NA in vitro and in vivo. We have shown that the incorporation of a folate-containing lipoconjugate (O-{2-[rac-2,3-di(tetradecyloxy)prop-1-yloxycarbonyl]aminoethyl}-O'-[2-(pteroyl-L-glutam-5-yl)aminoethyl]octadecaethyleneglycol) into the lipid composition (liposome F) provides targeted delivery to tumors that express FR at a high level [2,32]. In this study, we examined the in vivo toxicity of liposome F and the antitumor effect of combined antitumor therapy comprising MDR1targeted siRNA/F complexes and conventional polychemotherapy (PCHT) using tumor xenograft initiated in immunodeficient mice.…”

Lipophilic Polyamines as Promising Components of Liposomal Gene Delivery Systems

“…The highest transfection efficiency was exhibited by liposomes based on amphiphile 10c , which were superior to the efficiency of the commercial transfectant Lipofectamine 2000 (Thermo Fisher Scientific, Waltham, MA, USA) for any type of NAs transferred [ 42 , 43 ]. Targeted liposomes based on CA 10c were also successfully employed in vivo [ 44 , 45 , 46 , 47 , 48 , 49 ].…”