Specific targeting of phototoxic haptenated liposomes to a hapten-specific B cell lymphoma.
A method is reported to eliminate B lymphocytes specific for a haptenated lipid by using the lipid hapten to target a photosensitive drug to them. The photosensitizer eosin was coupled to a phospholipid and incorporated into trinitrophenol (TNP)-bearing small unilamellar vesicles of egg phosphatidylcholine (PC) and cholesterol in order to target the photosensitizer to B lymphoma cells (A20-HL) with TNP-specific membrane IgM receptors in vitro. Exposure of the treated cells to visible light led to an antigen-specific toxic effect indicated by inhibition of cell proliferation. A significantly higher concentration of liposomal eosin was required to inhibit control B cells. These were genetically identical B lymphoma cells (A20-2J) which lack only the DNA for the surface antigen receptor. Furthermore, pretreatment with TNP-conjugated keyhole limpet hemocyanin or anti-IgM antibody abolished the antigen-specific toxic effect, confirming that the TNP-targeted liposomal eosin mediates its effect by binding to the Ig antigen receptors on TNP-specific B cells. Incubation of cells with the TNP-bearing phototoxic liposomes at 4 degrees C instead of 37 degrees C did not alter the antigen-specific targeting effect, suggesting that uptake of the liposomal drug into the cells is not necessary for its toxic effect. Replacement of the liposomal phospholipid (egg PC) with saturated species of PC having higher phase transition temperatures or with sphingomyelin caused a decrease of the antigen-specific effect. These results demonstrate the potential use of antigen-bearing liposomal phototoxic drugs for the purpose of targeting and eliminating B cells with antigen-specific surface Ig receptors.
Avrilionis
K
K
Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Boggs
J M
JM
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002461:Cell Line, Transformed; D004801:Eosine Yellowish-(YS); D000939:Epitopes / Q000633:toxicity*; D006241:Haptens / Q000633:toxicity*; D018796:Immunoconjugates / Q000633:toxicity*; D008081:Liposomes / Q000276:immunology / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D010714:Phosphatidylethanolamines; D017319:Photosensitizing Agents / Q000276:immunology* / Q000633:toxicity; D010851:Picrates / Q000276:immunology; D017382:Reactive Oxygen Species; D011961:Receptors, Fc / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D006241:Haptens; D018796:Immunoconjugates; D008081:Liposomes; D010714:Phosphatidylethanolamines; D017319:Photosensitizing Agents; D010851:Picrates; D017382:Reactive Oxygen Species; D011961:Receptors, Fc; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C005858:picric acid; D004801:Eosine Yellowish-(YS)