Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells

摘要: Abstract A monoclonal antibody against the rat colon carcinoma CC531 was covalently coupled to liposomes containing a dipalmitoylated derivative of anticancer drug FUdR as prodrug in their bilayers. We investigated vitro interaction these with target cells and mechanism by which they deliver active intracellularly monitoring fate liposomal bilayer markers cholesterol-[14C]oleate [3H]cholesteryloleylether well 3H-labeled colloidal gold an encapsulated liposome marker. After binding immunoliposomes cell surface, only limited amounts were internalized demonstrated low level hydrolysis cholesterol ester morphological studies employing gold-labeled immunoliposomes. By contrast, already within 24 h immunoliposome-incorporated FUdR-dP hydrolyzed virtually completely parent intracellularly. This process inhibited variety endocytosis inhibitors, indicating that enters is processed involving endocytic process, resulting intracellular concentrations up 3000-fold higher than those medium. Immunoliposomes poly(ethyleneglycol) (PEG) chains on either directly or at distal end PEG able into tumor same rate without PEG. Based observations, we tentatively conclude during lipophilic selectively transferred surface subsequently constitutive pinocytic invaginations plasma membrane, thus ultimately delivering lysosomal compartment where release takes place. concept allows for efficient delivery liposome-associated need such be cells.