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Enhanced delivery to target cells by heat-sensitive immunoliposomes

Sullivan, Sean M. and Huang, Leaf (1986) Enhanced delivery to target cells by heat-sensitive immunoliposomes. Proceedings of the National Academy of Sciences of the United States of America, 83 (16). pp. 6117-6121. ISSN 0027-8424. PMCID PMC386450. doi:10.1073/pnas.83.16.6117.

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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.

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Additional Information:© 1986 by the National Academy of Sciences. Communicated by John D. Baldeschwieler, April 18, 1986. We thank Dr. R. Wohlhueter for his helpful discussions concerning nucleoside uptake properties. This work was supported by National Institutes of Health Grant CA 24553. L.H. is a National Institutes of Health Research Career Development Awardee (CA 00718). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
NIHCA 24553
NIHCA 00718
Subject Keywords:liposome targeting; controlled release
Issue or Number:16
PubMed Central ID:PMC386450
Record Number:CaltechAUTHORS:SULpnas86a
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10535
Deposited By: Tony Diaz
Deposited On:15 May 2008
Last Modified:08 Nov 2021 21:08

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