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Effects of Partially Thiolated Polycytidylic Acid and Liposomes on in Vitro Colony-forming Cells of Leukemic Mice

Departments of Biophysical Sciences [Y. K. H.] and Medicinal Chemistry [T. J. B.], State University of New York at Buffalo, Buffalo 14214, and Departments of Experimental Pathology [E. M.] and Medical Oncology [H. D. P.], Roswell Park Memorial Institute, Buffalo, New York 14263

Partially thiolated polycytidylic acid (MPC), an antileukemic agent, when administered to leukemic RF/UN mice inhibited the clonogenicity of bone marrow progenitor cells in a time-and dose-dependent manner. The effect of a single dose of MPC disappeared within 40 hr due to the rapid degradation of this compound in mice. When MPC was encapsulated in liposomes before injection, its activity at 19 hr after inoculation was similar to that of free MPC. The inhibitory effect of this liposome-MPC complex, however, persisted for at least 40 hr, indicating that the MPC was protected from hydrolysis by the nucleases present in blood. Drug-free liposomes increased the number of clonogenic progenitor cells, whereas a mixture of plain liposomes and MPC decreased the number of clonogenic cells to a greater extent than did MPC alone or MPC within liposomes. A possible explanation for these observations is that the liposomes per se altered the clearance function of the reticuloendothelial system and competed with MPC for uptake by the reticuloendothelial system cells, thereby resulting in increased plasma levels of MPC which in turn resulted in greater killing of the target cells.

¹ Recipient of Research Grant CH-20-I from the American Cancer Society.

² Leukemia Society of America Scholar. To whom requests for reprints should be addressed.

³ Recipient of CA 28494-01 from the National Cancer Institute, NIH.

⁴ Recipient of Grant CA-5834 from the National Cancer Institute, NIH.

Received 9/ 8/81. Accepted 1/ 5/82.