Delivery of interferon to intracellular pathways by encapsulation of interferon into multilamellar liposomes is independent of the status of interferon receptors

The antiproliferative effect of interferon alpha (IFN-α) against cultured 253J human bladder tumour cells was enhanced when IFN-α was encapsulated into multilamellar phospholipid liposomes (MLV). Moreover, significant cytostasis of a variant 253J subline (253Jα^R, resistant to the antiproliferative effect of IFN-α), could be achieved by delivery of IFN-α contained in liposomes. Although the two cell lines have the same number and affinity of cell receptors for IFN-α, the 253Jα^R cells did not down-regulate receptors as observed for the IFN-sensitive 253J cells. The IFN-response genes, 2′-5′ oligosynthetase and gene 6-16 were equally induced in both cell lines following incubation of the cells with either free IFN-α or liposome-encapsulated IFN-α. Incorporation of radiolabelled IFN-α into cells by liposomes was independent of the status of IFN-receptors (the receptors being either occupied or down-regulated). These observations are consistent with the hypothesis that the antiproliferative effects of IFN-α against 253J and 253Jα^R cells may be mediated by internalization of IFN-α.