Immunoliposomes as an Efficient and Target-specific Carrier for Antitumor Drugs 1

pH-sensitive immunoliposomes composed of dioleoylphosphatidylethanolamine and oleic acid (8:2) significantly enhanced the cytotoxic effect of the entrapped drug 1-0-D-arabinofuranosylcytosine (ara-C) to target L-929 cells, as compared to free drug, drug encapsulated in antibody-free liposomes, or in pH-insensitive immunoliposomes. These pH-sensitive immunoliposomes were ineffective against nontarget A-3I cells. The enhanced cytotoxic effect could be blocked by excess free antibody or excess drug-free immunoliposomes. Pretreatment of target cells with the weak bases chloroquine or M I4( I. which raise the internal pH of cellular acidic organelles such as endosomes and lysosomes, inhibited the cell killing activity of ara-C encapsulated in the pH-sensitive immunoliposomes. Since it is known that ara-C is rapidly inactivated in the lysosomes, our results suggest that the release of ara-C from the pHsensitive immunoliposomes occurs in a prelysosomal compartment, i.e.. the endosÃ3me. Parallel experiments using methotrexate as a cytotoxic drug confirm the enhanced ability of the pH-sensitive liposomes for cytoplasmic drug delivery over that of free drug. These results indicate that pH-sensitive immunoliposomes can be used as an efficient and targetspecific carrier for antitumor drugs.

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