The receptor-mediated assimilation of low density lipoprotein (LDL) by many cancer cells is much higher than that of normal cells. This fact suggests that lipoproteins with incorporated cytotoxic drugs may be used as a carrier for chemotherapeutic agents to neoplastic cells. In this study a lipophilic cytotoxic compound is incorporated into reconstituted LDL by two different methods. Both the structure and cellular uptake were found to be similar to those of native LDL. Tests of the cytotoxic activity on cultured cells demonstrated that the drug delivered to the cells via the LDL pathway was able to kill 100% of the cells. Heparin and a low temperature, which are known to inhibit uptake of LDL by the receptor mechanism, abolished the cytotoxic activity of the drug-lipoprotein conjugates. The results suggest that it may be possible to use reconstituted LDL as a vehicle for lipophilic antineoplastic drugs in order to increase the drug accumulation and selectivity in tumor cell populations with high LDL receptor activity.

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Supported by grants from The Cancer Society of Finland.

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