[en] Cis-diamminedichloroplatinum II (cisplatin) heavily or lightly loaded (fluid, solid, negatively charged or neutral) liposomes were prepared. Cisplatin release from liposomes was observed only after long dialysis times or after liver lysosomal enzymatic disintegration in solution. Mouse Ehrlich tumor cells (ELT) cultured in vitro were treated with cisplatin, liposomes or cisplatin loaded liposomes, and the effects on the mitotic activity, the DNA content and the ultrastructure were compared. Cisplatin (1-10 micrograms/ml) had an antimitotic activity and modified the DNA content in ELT cells. Ribosome aggregation, perichromatin or interchromatin granule accumulation, and chromatin condensation or some degree of dispersion could be observed. Negatively charged fluid liposomes had an antimitotic activity and modified the DNA content in ELT cells at lower concentrations (0.3 mumoles/ml) than in the case of neutral fluid liposomes (1.5 mumoles/ml). Negatively charged solid liposomes were not toxic at these concentrations. Ultrastructural analysis of ELT cells treated in vitro with negatively charged fluid liposomes revealed their extracellular adsorption and their disintegration in phagolysosomes. A fusion between liposomes and the plasma membrane was not definitely demonstrated. Cisplatin loaded liposomes also had an antimitotic activity and modified the DNA content in ELT cells. These effects were similar to or more pronounced than those induced by free cisplatin. Ultrastructural analysis revealed some kind of electron dense material in phagolysosomes which was never observed after the treatment with free cisplatin or liposomes alone. Effects on nucleic acids were rarely observed.
De Pauw-Gillet, Marie-Claire ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie - Département des sciences biomédicales et précliniques
Heinen, Ernst ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine
Weber, Géraldine ; Centre Hospitalier Universitaire de Liège - CHU > Médecine de l'appareil locomoteur
Bassleer, Roger ; Université de Liège - ULiège > Relations académiques et scientifiques (Médecine)
Language :
English
Title :
Effects of cis-diamminedichloroplatinum (II) loaded liposomes on mouse Ehrlich tumor cells.
Macquet, Butour, Johnson (1983) Physicochemical and structural studies on the in vitro interactions between Pt (II) compounds and DNA. ACS Symp Ser 209:75-100.
Hitchock, Lock, Pratt, Lippert (1983) Platinum complexes with DNA bases nucleotides and DNA. ACS Symp Ser 209:209-227.
Heinen, Bassleer (1976) Cytological and cytochemical analysis of the effects of cis-dichlorodiamminoplatinum (II) on thick fibroblasts cultivated in vitro. Chemother 22:253-261.
Heinen, Bassleer (1976) Mode of action of cis-dichlorodiamine platinum (II) on mouse Ehrlich ascites tumor cells. Biochem Pharmacol 25:1871-1875.
de Duve (1961) Lysosomes and chemotherapy. Biological Approaches in Cancer Chemotherapy , R Harris, Academic Press, London; 101-112.
Heinen, Desaive, Houssier, Gillet, Chèvremont (1976) Effets due complexe cis-dichloro-diammino-platine (II) — acide désoxyribonucléique sur des cellules normales ou cancéreuses. C R Soc Biol 170:919-921.
De Pauw-Gillet, Houssier, Fredericq (1979) Interaction of DNA and purine nucleosides with cis-dichlorodiammineplatine (II) and antimitotic activity of the complexes on meristematic root cells. Chem Biol Interact 25:87-102.
Gregoriadis, Senior, Trouet (1982) “Targeting of drugs” NATO Advanced Study Institutes. Life Sci , Ser A; 47.
Kaledin, Matienko, Budker, Nikolin, Gruntenko (1978) Inhibiting effect of cis-diamminodichloro platinum incorporated into liposomes on lymphogenic metastases of transplantable tumors in mice. Dokl Acad Nauk SSR 242:473-476.
Yatvin, Mühlensiepen, Porschen, Feinendegen, Weinstein (1981) Selective delivery of liposome-associated cis-dichloro-diammine platinum (II) by heat and its influence on tumor drug uptake and growth. Cancer Res 41:1602-1607.
Gruntenko, Nikolin, Matienko, Kaledin, Vakrusheva, Budker (1982) Liposomes as carriers of antineoplastic drugs in the treatment of neoplastic liver lesions. Dokl Akad Nauk SSSR 265:225-228.
Golla, Ayres (1973) Spectrophotometric determination of platinum with O-phenylenediamine. Talenta 20:199-210.
Weber, Robaye, Delbrouck, Roelandts, Didberg, Bartsch, De Pauw (1980) Biomedical application of P.I.X.E. in University of Liège. Nucl Instrum Meth 168:551-556.
Raz, Bucana, Fogler, Poste, Fidler (1981) Biochemical, morphological and ultrastructural studies in the uptake of liposomes by murine macrophages. Cancer Res 41:487-494.
Lewis, Knight Practical Methods in Electron Microscopy , A Glauert, North-Holland, Amsterdam, Part I; 1977, 5:112.
Lewis, Knight Practical Methods in Electron Microscopy , A Glauert, North-Holland, Amsterdam, Part I; 1977, 5:118.
Lewis, Knight Practical Methods in Electron Microscopy , 2nd edn., A Glauert, North-Holland, Amsterdam, Part I; 1977, 5:119.
Heinen (1977) Mode d'action d'agents antimitotiques, en particulier d'agents liés à des macromolécules, sur des fibroblastes embryonnaires, des macrophages péritonéaux et des cellules tumorales d'Ehrlich. Thèse de Doctorat en Sciences biomédicales expérimentales, 2nd edn., Université de Liège; .
Gregoriadis Transfer of Cells Constituents into Eukariotic Cells , J Celis, A Graessmann, A Loyter, Plenum, New York; 1980, 173-199.
Roberts, Fraval (1980) Repair of cis-platinum (II) diammine dichloride-induced DNA damage and cell sensitivity. Cisplatin Current Status and New Developments , A Prestayko, S Crooke, Academic Press, London; 57-78.
De Pauw-Gillet, Heinen, Houssier, Fredericq, Bassleer (1982) Effets du cis-dichlorodiammineplatine (II) (cis-Pt II) sur l'ultrastructure de la chromatine de cellules animales ou végétales et répercussions sur le cycle cellulaire. C R Soc Biol 176:364-368.
Sodhi (1977) Origin of giant cells in regressing sarcoma-180 after cis-dichlorodiammine platinum (II) treatment: a fine structural study. J Clin Hematol Oncol 7:569-579.
Daskal, Prestayko, Crooke (1980) Morphological manifestations of cisplatin analogs in rats: an ultrastructural study. Cisplatin Current Status and New Developments , A Prestayko, S Crooke, Academic Press, London; 249-269.
Houssier, De Pauw-Gillet, Hacha, Fredericq (1983) Alterations in the nucleosome and chromatin structures upon interaction with platinum coordination complexes. Biochim biophys Acta 739:317-325.
Thompson, Arquilla, Simpkins (1982) The interaction of platinum complexes with nucleosomes investigated with fluorescent probes. Biochim biophys Acta 698:173-182.
Lippard (1980) Binding of a platinum antitumor drug to its likely biological targets. Inorg Chem Biol Med 9:148-156.
Harrap, Jones, Wilkinson, Clink, Sparrow, Mitchley, Clarke, Veasey (1980) Antitumor, toxic and biochemical properties of cisplatin and eight other platinum complexes. Cisplatin Current Status and New Developments , A Prestayko, S Crooke, Academic Press, London; 193-212.
Behrens, Yamamoto, Brown, Bryan (1979) Cytotoxicity of liposomes towards cultured human and rat bladder cancer cell lines. Proc Am Assoc Cancer Res , 2nd edn.; 20:160.
Poste, Papahadjopoulos (1976) Lipid vesicles as carriers for introducing materials into cultured cells: influence of composition on mechanisms of vesicles incorporation into cells. Proc Natl Acad Sci USA , 2nd edn.; 73:1603-1607.
Pagano, Weinstein (1978) Interactions of liposomes with mammalian cells. Ann Rev Biophys Bioeng 7:435-468.
Allen, McAllister, Mausolf, Gyorffy (1981) A study of the interactions of liposomes containing entrapped anti-cancer drugs with the EMT6, S49 and AE1 (transport deficient) cell lines. Biochem biophys Acta 643:346-362.
Lhoest-Gauthier, De Pauw-Gillet, Van Ophem, Bassleer (1984) Effets de composés d'or libres ou incorporés dans des liposomes sur des cellules synoviales humaines en culture. Arch Biol 95:413-421.
Razi, Otiro, Sadler (1983) Ligang exchange reactions of gold drugs in model systems and in red cells. Am Chem Soc 19:371-384.