AMD3100 conjugates as components of targeted nonviral gene delivery systems: synthesis and in vitro transfection efficiency of CXCR4-expressing cells.

We describe the synthesis of a series of AMD3100-lipid and AMD3100-polycationic conjugates which were used as components of targeted lipoplexes (in conjunction with (poly)cationic lipids) and polyplexes, respectively, for mediating specific gene transfer into cells expressing CXCR4 which displays a high affinity for AMD3100. Transfection studies were investigated with suspension CXCR4(+) human lymphoma Jurkat cells and with adherent CXCR4(-) human glioblastoma T98G and human lung carcinoma A549 cells lines in order to demonstrate a receptor-mediated endocytosis pathway and to minimize nonspecific transfection pathways. Altogether, our results show that polyplexes formulated with AMD-labeled polymers constitute, under certain conditions, specific gene transfer systems into suspension CXCR4(+) Jurkat cells.

Polycationic telomers and cotelomers for gene transfer: synthesis and evaluation of their an vitro transfection efficiency.

We report on the synthesis of a series of lipopolyamine telomers, [I(Asp)-14,n(A)(NH), I(His)-18,n(A)(NH), I-18,n(B)(NMe), Gal-n(A)(NH)], and random cotelomers, [I-18,n(A)(NH)-n(B)(NMe) and I-18,n(A)(NH)-n(C)(OH)], and on their in vitro gene transfer capability. They were obtained by a telomerization process of various amino-acrylamide taxogens with various lipophilic thiol telogens which might also contain an aspartic or a histidine residue or with a thiogalactosyle derivative. For N/P ratios (N = number of (co)telomer amine equivalents, P = number of DNA phosphates) from 0.

Lipopolycationic telomers for gene transfer: synthesis and evaluation of their in vitro transfection efficiency.

We report on the synthesis of a series of lipopolyamine telomers I-14,n, I-18,n, and II-18,n and on their in vitro gene-transfer capability. Their structure consists of a polyamine polar moiety, including n primary amine functions (from 1 to 70), connected to a hydrophobic moiety, including two hydrocarbon C14 or C18 chains, through a mercaptopropanoyl or mercaptoglyceryl unit and an amide or ether function. They were obtained by telomerization of N-[2-[(BOC)aminoethyl]]acrylamide with N,N-ditetradecyl- and N,N-dioctadecylpropanamide-3-thiol and rac-1,2-dioctadecyloxypropane-3-thiol, respectively, then BOC deprotection.