Preparation and characterization of heat-sensitive immunoliposomes.
Immunoliposomes able to bind specifically to target cells and to release their encapsulated contents upon brief heating were prepared. Monoclonal anti-H2Kk was covalently derivatized with palmitic acid by the method of Huang, A. et al. (Huang, A., Tsao, Y.S., Kennel, S.J. and Huang, L. (1982) Biochim. Biophys. Acta 716, 140-150). The palmitoyl antibody was injected at a controlled rate into a suspension of fused unilamellar dipalmitoylphosphatidylcholine liposomes maintained at a constant temperature. The final protein-to-lipid ratio of the resultant liposomes with incorporated antibody (immunoliposomes) was dependent upon the rate of antibody injection and the lipid concentration. Injection of palmitoyl antibody into a liposome suspension containing 50 mM carboxyfluorescein at 41 degrees C resulted in simultaneous antibody incorporation and entrapment of dye. Immunoliposomes were able to release the entrapped carboxyfluorescein upon heating. The release of dye at temperatures between the pre- and main-transition temperatures of DPPC was abolished by the addition of calf serum (5%). Furthermore, the presence of serum resulted in an increase in the temperature of the maximal release rate and also in the rate of release at that temperature. Retention of antigen-binding capacity was demonstrated by the ability of the immunoliposomes to bind specifically to the target cells. Rapid release of entrapped carboxyfluorescein from immunoliposomes bound to target cells at 4 degrees C was achieved upon brief exposure (less than 3 min) at 41 degrees C. These heat-sensitive immunoliposomes may be useful in enhancing drug delivery to target cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D005452:Fluoresceins / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology; D006358:Hot Temperature; D008081:Liposomes / Q000276:immunology*; D008433:Mathematics; D051379:Mice; D008854:Microscopy, Electron
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005452:Fluoresceins; D006183:H-2 Antigens; D008081:Liposomes; C024098:6-carboxyfluorescein