Incorporation of cis-dichlorobiscyclopentylamineplatinum (II) into liposomes enhances its uptake by ADJ/PC6A tumour cells: comparative effects of the free and liposome-incorporated drug on the cyclic 3'-5' nucleotide phosphodiesterase activity.

ADJ/PC6A tumour cells in tissue culture can incorporate large amounts of 14C-cholesterol-labeled liposomes prepared by phosphatidylcholine: cholesterol: phosphatidic acid (7:2:1 molar proportions) without cytotoxic effects. Fusion of liposomes with the cell plasma membrane may represent an important pathway for lipid incorporation. The incorporation of the antitumour drug cis-dichlorobiscyclopentylamineplatinum (II) in these liposomes greatly enhances its cytotoxicity against ADJ/PC6A tumour cells. Cis-dichlorobiscyclopentylamineplatinum (II) incorporate into liposomes caused a two-fold elevation of cyclic AMP as compared to the free drug in ADJ/PC6A tumour cells, 24 h after treatment with a dose of 0.2 micrograms/ml. Liposomes containing cis-dichlorobiscyclopentylamineplatinum (II) at concentrations as low as 0.6 micrograms/ml effectively inhibited (approximately 70%) the activity of cyclic AMP-phosphodiesterase, which was used as functional parameter in this study. Similar inhibition of the enzyme activity by the free drug was achieved only at concentrations as high as 5 micrograms/ml. It is suggested that the incorporation of cis-dichlorobiscyclopentylamineplatinum (II) into liposomes offers a potentially useful tool for enhancing the cytotoxicity of the drug.