LIPOSOME-CELL INTERACTIONS IN-VITRO - EFFECT OF LIPOSOME SURFACE-CHARGE ON THE BINDING AND ENDOCYTOSIS OF CONVENTIONAL AND STERICALLY STABILIZED LIPOSOMES

The cellular uptake of liposomes is generally believed to be mediated by adsorption of liposomes onto the cell surface and subsequent endocy tosis. This report examines the effect of liposome surface charge on l iposomal binding and endocytosis in two different cell lines: a human ovarian carcinoma cell line (HeLa) and a murine derived mononuclear ma crophage cell line (J774), The large unilamellar liposomes were compos ed of 1,2-dioleolyl-sn-glycero-3-phosphatidylcholine with and without the addition of either a positively charged lipid, 1,2-dioleoyl-3-dime thylammonium propanediol (DODAP), or a negatively charged lipid, 1,2-d ioleolyl-sn-glycero-3-phosphatidylserine. In some experiments 5 mol% o f the anionic PEG(2000)-PE or a neutral PEG lipid of the same molecula r weight was added. HeLa cells were found to endocytose positively cha rged liposomes to a greater extent than either neutral or negatively c harged liposomes. This preference was not lipid-specific since inclusi on of a cationic cyanine dye, DiIC18- (3), to impart positive charge i n place of DODAP resulted in a similar extent of endocytosis. In contr ast the extent of liposome interaction with J774 cells was greater for both cationic and anionic liposomes than for neutral liposomes. The g reater uptake of positively charged liposomes by HeLa cells was also o bserved with sterically stabilized liposomes (PEG liposomes). Although the overall amount of endocytosis for all the PEG liposomes examined was attenuated relative to conventional liposomes, the extent of endoc ytosis was greatest for positively charged PEG liposomes, whereas nega tively charged PEG(2000)-PE liposomes were hardly endocytosed by the H eLa cells. Incorporation of a neutral PEG lipid into liposomes permits the independent variation of liposome steric and electrostatic effect s in a manner that may allow interactions with cells of the reticuloen dothelial system to be minimized, yet permit strong interactions betwe en liposomes and proliferating cells.