Use of mannosylated liposomes for in vivo targeting of a macrophage activator and control of artificial pulmonary metastases.
From a mannosylated mycobacterial phospholipid, we prepared an original type of liposome which was taken up by macrophages by means of the mannose/fucose receptor. When a lipophilic immunomodulator, MDP-L-alanyl-cholesterol (MTP-CHOL) was included in such liposomes, they were able to activate WAG rat alveolar macrophages for cytotoxicity against syngeneic tumour cells in vitro. The presence of suboptimal levels of endotoxin was essential for this activation. Cytotoxic macrophages could also be induced in vivo by injecting immunomodulator-loaded liposomes intravenously 24 h before harvesting macrophages. A decrease in experimental pulmonary colonies arising from i.v. injected tumour cells was observed following repeated administration of such liposomes.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D002788:Cholesterol Esters / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D037181:Lectins, C-Type; D008081:Liposomes / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000187:drug effects
D002788:Cholesterol Esters; D037181:Lectins, C-Type; D008081:Liposomes; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C047489:N-acetylmuramyl-alanyl-isoglutamine-alanyl-cholesterol