Antitumoral properties and reduced toxicity of LPS targeted to macrophages via normal or mannosylated liposomes.

Neo-mannosylated liposomes have been prepared by coupling a mannose derivative bearing a hydrophilic spacer arm to preformed large unilamellar liposomes containing 4-(p-maleimidophenyl) butyryl-phosphatidylethanolamine. Lipopolysaccharide (LPS) was encapsulated in normal or neo-mannosylated liposomes; the neo-mannosylated vesicles showed specificity for the in vitro activation to toxicity of macrophages only in the case of differentiated macrophages presenting mannose receptors at their surface. In vivo, LPS entrapped in neo-mannosylated vesicles showed a reduced toxicity for animals hypersensitive to LPS. Moreover targeting of LPS to tissue macrophages with neo-mannosylated liposomes induced regression of experimental solid tumors in mice (EMT6 sarcoma, 3LL carcinoma) and was effective on lung metastases.