AdvisorO'Brien, David F.
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PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractBennett and O'Brien [Biochemistry 1995 34, 3102] showed that the ultraviolet light exposure of two-component large unilamellar liposomes (LUV) composed of a 3:1 molar mixture of dioleoylphosphatidylethanolamine (DOPE) and 1,2-bis[10-(2'-hexadienoyloxy)-decanoyl]-sn-glycero-3-phosphatidylcholine (bis-SorbPC) facilitated liposome fusion. The rate and extent of fusion was dependent on the extent of photopolymerization, the temperature, and the pH. Here, the effect of the molar lipid ratio of DOPE/bis-SorbPC liposomes on the temperature for the onset of fusion, was characterized by changing the relative amounts of unreactive polymorphic lipid, and reactive lamellar lipid. The cellular uptake of liposomes is mediated by nonspecific adsorption of liposomes onto the cell surface and subsequent endocytosis. This research compared the effect of liposome surface charge on liposomal binding and endocytosis by a human cancer cell line, HeLa, and a murine macrophage cell line, J774. LUV were composed of dioleolylphosphatidylcholine with and without either a cationic lipid, dioleoyldimethylammonium propanediol, or an anionic lipid, dioleolylphosphatidylserine. HeLa cells endocytosed cationic liposomes to a greater extent than either neutral or anionic liposomes and with PEG- LUV, a neutral PEG-lipid over the anionic PEG-PE2000. In contrast, the extent of liposome endocytosis by J774 cells was quite similar for both cationic and anionic liposomes, both greater than neutral liposomes. Incorporation of a neutral PEG lipid may minimize interactions with cells of the RES, yet strongly interact with proliferative cells. Clapp et al., [Macromolecules 1997 30, 32] demonstrated that certain amphiphilic cyanine dyes are capable of sensitizing lipid polymerization to visible light. The individual effects of pH, light intensity, temperature, and the requirement for oxygen suggested that the polymerization process is initiated by electron transfer from the dye excited state to oxygen, to yield superoxide anion, which in aqueous media combines to form hydrogen peroxide. Here, irradiation of cell-associated visible light sensitive liposomes sensitized with either the cationic dye, N, N' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine, DiIC(18)3, or a sulfonated derivative, DiI-DS, caused cell membrane damage and cytoplasmic delivery of liposomal contents could not be confirmed.
Degree ProgramGraduate College