Enhanced delivery to target cells by heat-sensitive immunoliposomes.
Heat-sensitive immunoliposomes are capable of releasing the entrapped content at the target cell surface upon a brief heating to the phase transition temperature of the liposome membrane. In this study we have examined the delivery efficiency of drugs entrapped in heat-sensitive immunoliposomes. Immunoliposomes composed of dipalmitoyl phosphatidylcholine with entrapped [3H]uridine were incubated with target cells at 4 degrees C. The cell-liposome mixture was then heated to 41 degrees C and the uptake of [3H]uridine into the intracellular pool of phosphorylated uridine-containing molecules was measured. The immunoliposomes showed maximal release of the uridine at 41 degrees C, the phase transition temperature of dipalmitoyl phosphatidylcholine liposomes. The largest accumulation of [3H]uridine in the target cells also took place at 41 degrees C. The initial level of uptake of [3H]uridine released from immunoliposomes by heating was greatly enhanced over that observed for free [3H]uridine and [3H]uridine released from liposomes without attached antibody. The nucleoside uptake inhibitors nitrothiobenzylinosine, dipyridamole, and unlabeled uridine were able to inhibit uptake of [3H]uridine released from immunoliposomes. This supports the hypothesis that the enhanced uptake is due to a heat-induced release of [3H]uridine at the cell surface followed by transport and phosphorylation of [3H]uridine by the target cells. These results indicate the feasibility of using the heat-sensitive immunoliposomes as a target-specific drug delivery system.
Sullivan
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Huang
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001692:Biological Transport; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology; D006358:Hot Temperature; D007074:Immunoglobulin G; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage*; D010766:Phosphorylation; D011663:Pulmonary Surfactants / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007074:Immunoglobulin G; D008081:Liposomes; D011663:Pulmonary Surfactants; D014529:Uridine