Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo

Purpose, The purpose of this study was to determine the usefulness of trans ferrin (TF)-pendant-type polyethyleneglycol (PEC)-liposomes (TF-PEG-liposom es), in which TF was covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes as a carrier for in vivo cytoplas mic targeting to tumor cells. Methods. Small unilamellar TF-PEG-liposomes (100-140 nm diameter) were prep ared from DSPC. CH. DSPE-PEG, and DSPE-PEG-COOH (2:1:0.11:0.021. molar rati o), and were conjugated to TF via the carboxyl residue of DSPE-PEG-COOH. Th e intracellular targeting ability of TF-PEG-liposomes to tumor cells was ex amined in vitro and in Colon 26 tumor-bearing mice. Results, TF-PEG-liposomes, bearing approximately 25 TF molecules per liposo me. readily bound to mouse Colon 26 cells in vitro and were internalized by receptor-mediated endocytosis. TF-PEG-liposomes showed a prolonged residen ce time in the circulation and low RES uptake in Colon 26 tumor-bearing mic e, resulting in enhanced extravasation of the liposomes into the solid tumo r tissue. Electron microscopic studies in Colon 26 tumor-bearing mice revea led that the extravasated TF-PEG-liposomes were internalized into tumor cel ls by receptor-mediated endocytosis. Conclusion. TF-PEG-liposomes had the capabilities of specific receptor bind ing and receptor-mediated endocytosis to target cells after extravasation i nto solid tumors in vitro. Such liposomes should he useful for in vivo cyto plasmic targeting of chemotherapeutic agents or plasmid DNAs to target cell s.