Oligonucleotide-liposomes can be targeted to specific cells via covalently coupled antibodies to cell surface markers. Neutral lipid-coated cationic liposomes encapsulating antisense oligonucleotides against c-myb and targeted to disialoganglioside, GD2, were much more effective in inhibiting the growth of neuroblastoma cells compared to nontargeted liposomes and free oligonucleotides (119). These liposomes also had significant antitumor effects in vivo, but part of this effect could be attributed to the immunostimulatory effect of CpG sequences in the oligonucleotide (120). GD2-targeted coated cationic liposomes containing anti-c-myc oligonucleotides inhibited melanoma cell proliferation, the development of microscopic metastases, and tumor growth (121).
Coated cationic liposomes encapsulating antisense oligonucleotides against the mRNA of the P-glycoprotein can be targeted to multidrug-resistant B-cell lymphoma cells via the attachment of anti-CD19 antibodies to the liposomes (122). Coated cationic liposomes targeted to scavenger receptors via aconitylated human serum albumin accumulated in liver endothelial cells and could downregulate intercellular adhesion molecule-1 mRNA in the macrophage cell line J774 (123).
Although antibody coupling to PEG-DSPE has the advantage that the targeting ligand protrudes out from the liposome surface, the inhibitory effect of this polymeric lipid on transfection (124,125) should be taken into consideration. Thus, it may be necessary to incorporate exchangeable PEG-lipids into the cationic vector (5,124,126,127). Utilizing such a system termed "programmable fusogenic vesicles'' with exchangeable PEG-ceramides, Hu et al. (127) showed a relatively modest reduction in bcl-2 mRNA levels in 518A2 melanoma cells, whereas control oligonucleotides with reverse polarity resulted in an increase in mRNA levels. PEGylated cationic liposomes targeted to HER-2 and complexed with an oligonucleotide antisense to the Bcl-2 protein reduced protein expression by about 50% in BT-474 breast carcinoma cells, while the nontargeted liposomes were not effective (117).
In another targeting approach, Rodriguez et al. (128) utilized biotiny-lated antibodies to p185/HER-2, which is overexpressed on breast cancer cells, and associated them with cationic liposomes containing streptavidin-DOPE:DOTAP complexed with an antisense oligonucleotide directed toward the translational start site of dihydrofolate reductase RNA. As an alternative, they associated streptavidin to biotinylated antibody and biotinylated oligonucleotide that was complexed with DOTAP. The immu-noliposomes were more toxic to SKBR3 cells that overexpress p185 than the antisense oligonucleotide in the absence of the antibody. Antisense oligonu-cleotides against HER-2 mRNA complexed with folate-targeted liposomes inhibited cell growth and HER-2 expression in SCC-2CP head and neck tumor cells, induced apoptosis, and increased the sensitivity of the cells to chemotherapeutic agents (129).
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Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.