Pegylation of Liposomes in Cell-Specific Targeting: It Does Not Always Make Sense

  • Gerrit L. Scherphof
  • Gerben A. Koning
  • Jan A. A. M. Kamps
  • Toos Daemen
Part of the NATO ASI Series book series (NSSA, volume 300)


Four studies on the use of PEG-ylated liposomes in delivery to liver-associated cells are presented in this paper: (1) hepatocyte-directed delivery; (2) alleviation of Kupffer cell toxicity caused by liposomal doxorubicin; (3) immunospecific delivery to intrahepatic colon tumor cells; (4) scavenger receptor-mediated delivery to hepatic endothelial cells.


Kupffer Cell Liposomal Doxorubicin Liposome Size PEGylated Liposome Liver Endothelial Cell 
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  1. Chu, C.-J. and Szoka, F.C., 1994, pH-Sensitive liposomes, J. Liposome Res. 4:361.CrossRefGoogle Scholar
  2. Daemen, T., Hofstede, G., Ten Kate, M.T., Bakker-Woudenberg, I.A.J.M. and Scherphof, G.L., 1995, Liposomal doxorubicin induced toxicity: impairment of phagocytic activity and depletion of liver macrophages, Int. J. Cancer, 61:716.PubMedCrossRefGoogle Scholar
  3. Daemen, T., Regts, J., Meesters, M., Ten Kate, M.T., Bakker-Woudenberg, I.A.J.M. and Scherphof, G.L., 1997a, Toxicity of doxorubicin entrapped within long-circulating liposomes, J. Control. Release, 44:1.CrossRefGoogle Scholar
  4. Daemen, T., Velinova, M., Regts, J., De Jager, M., Kalicharan, R., Donga, J., Van der Want, J.J.L. and Scherphof, G.L., 1997b, Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat, Hepatology. 26:416.PubMedCrossRefGoogle Scholar
  5. Daleke, D.L., Hong, K. and Papahadjopoulos D., 1990, Endocytosis of liposomes by macrophages: binding, acidification and leakage of liposomes monitored by a new fluorescence assay, Biochim. Biophys. Acta, 1024:352.PubMedCrossRefGoogle Scholar
  6. Derksen, J.T.P. and Scherphof G.L., 1985, An improved method for the covalent coupling of proteins to liposomes, Biochim. Biophys. Acta, 814:151.CrossRefGoogle Scholar
  7. Dingemans, K.P., Van den Berg Weerman, M.A., Keep, R.F. and Das P.K., 1994, Developmental stages in experimental liver metastases: relation to invasiveness, Int. J.Cancer, 57:433.PubMedCrossRefGoogle Scholar
  8. Goebel, F.-D., Goldstein, D., Goos, M., Stewart, J.S., 1996, Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi’s sarcoma, Brit. J. Cancer, 73:989.PubMedCrossRefGoogle Scholar
  9. Heuff, G., Oldenburg, H.S.A., Boutkan, H., Visser, J.J., Beelen, R.H.J., Van Rooijen, N., Dijkstra, C.D. and Meyer, S., 1993, Enhanced tumor growth in the rat liver after selective elimination of Kupffer cells, Cancer Immunol. Immunother., 37:125.PubMedCrossRefGoogle Scholar
  10. Ishibashi, S., Herz, J. Maeda, N., Goldstein, J.L. and Brown, M.S., 1994, The two-receptor model of lipoprotein clearance: tests of the hypothesis in “knock-out” mice lacking the low density lipoprotein receptor, apolipoprotein E or both proteins, Proc. Natl. Acad. Sci. USA, 89:4431.CrossRefGoogle Scholar
  11. Jansen, R.W., Olinga, P., Harms, G. and Meijer, D.K.F., 1993, Pharmacokinetic analysis and cellular distribution of the anti-HIV compound succinylated human serum albumin in vivo and in the isolated perfused rat liver, Pharmaceut. Res. 10:1611.CrossRefGoogle Scholar
  12. Kamps, J.A.A.M., Morselt, H.W.M., Swart, P.J. Meijer, D.K.F. and Scherphof G.L., 1997, Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells, Proc. Natl. Acad. Sci. USA, 94:11681.PubMedCrossRefGoogle Scholar
  13. Kamps, J.A.A.M., Swart, P.J., Morselt, H.W.M., Pauwels, R., De Béthune, M.P., De Clercq, E., Meijer, D.K.F. and Scherphof, G.L., 1996, Preparation and characterization of conjugates of (modified) human serum albumin and liposomes: drug carriers with an intrinsic anti-HIV activity. Biochim. Biophys. Acta, 1278:183.PubMedCrossRefGoogle Scholar
  14. Kuipers, F., Spanjer, H.H., Havinga, R., Scherphof, G.L. and Vonk, R.J., 1986, Lipoproteins and liposomes as in vivo cholesterol vehicles in the rat: preferential use of cholesterol carried by small unilamellar liposomes for the formation of muricholic acids. Biochim. Biophys. Acta, 876:559.PubMedCrossRefGoogle Scholar
  15. Landschulz, K.T., Pathak, R.K., Rigotti, A., Krieger, M. and Hobbs H.H., 1996, Regulation of a scavenger receptor class B, type I, a high density lipoprotein receptor in liver and steroidogenic tissues of the rat, J. Clin. Invest., 98:984.PubMedCrossRefGoogle Scholar
  16. Roerdink, F.H., Regts, J., Van Leeuwen, B. and Scherphof G.L., 1984, Intrahepatic uptake and processing of small unilamellar vesicles in rats, Biochim. Biophys. Acta, 770:195.PubMedCrossRefGoogle Scholar
  17. Scherphof, G.L. and Kamps, J.A.A.M., 1998, Receptor vs. non-receptor mediated clearance of liposomes, Adv. Drug Deliv. Rev., in press.Google Scholar
  18. Scherphof, G.L., Morselt, H. and Allen, T.M., 1994, Intrahepatic distribution of long-circulating liposomes containing poly(ethyleneglycol) distearoylphosphatidylethanolamine. J. Liposome Res., 4:213.CrossRefGoogle Scholar
  19. Scherphof, G.L. and Crommelin D.J.A., 1996, Cells involved in removing liposomes from the blood circulation: why are they so special?, J. Liposome Res., 6:19.CrossRefGoogle Scholar
  20. Scherphof, G.L., Kamps, J.A.A.M. and Koning, G.A., 1997, In vivo targeting of surface-modified liposomes to metastatically growing colon carcinoma cells and sinusoidal endothelial cells in the rat liver, J. Liposome Res., 7:419.CrossRefGoogle Scholar
  21. Spanjer, H.H., Van Galen, M., Roerdink, F.H., Regts, J. and Scherphof, G.L., 1986, Intrahepatic distribution of small unilamellar liposomes as a function of liposomal lipid composition, Biochim. Biophys. Acta, 863:224.PubMedCrossRefGoogle Scholar
  22. Steinberg, D., 1996, A docking receptor for HDL cholesterol ester, Science 271:460.PubMedCrossRefGoogle Scholar
  23. Uziely, B., Jeffers, S., Isacson, R., Kutsch, K., Wei-Tsao, D., Yehoshua, Z., Libson, E., Muggia, F.M. and Gabizon, A., 1995, Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies, J. Clin. Oncol., 13:1775.Google Scholar
  24. Verkade, H.J., Zaal, K.J., Derksen, J.T.P., Vonk, R.J., Hoekstra, D., Kuipers, F. and Scherphof G.L., 1992, Processing of the phospholipid analog Rhodamine-PE by rat hepatocytes in vitro and in vivo, Biochem. J., 284:259.PubMedGoogle Scholar
  25. Zalipsky, S., Puntambekar, B., Boulikas, P., Engbers, CM. and Woodle, M.C., 1995, Peptide attachment to extremities of liposomal surface-grafted PEG chains: preparation of the long-circulating form of laminin pentapeptide YIGSR, Bioconjug. Chem., 6:705.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Gerrit L. Scherphof
    • 1
  • Gerben A. Koning
    • 1
  • Jan A. A. M. Kamps
    • 1
  • Toos Daemen
    • 1
  1. 1.Department of Physiological Chemistry, Groningen Institute for Drug StudiesUniversity of Groningen, Medical SciencesGroningenThe Netherlands

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