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Interaction of Differently Designed Immunoliposomes with Colon Cancer Cells and Kupffer Cells. An in Vitro Comparison

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Abstract

Purpose. Evaluate the effectiveness of distal-end coupling of a tumor-specific antibody to liposomal polyethylene glycol (PEG) chains to improve target binding and reduce interference by macrophage uptake.

Methods. Monoclonal antibody CC52, specific for CC531 rat colon carcinoma, was coupled to the bilayer of PEG-liposomes (type I) or to the distal end of bilayer-anchored PEG-chains (type II). Uptake of both (radiolabeled)liposome types by CC531 cells and rat liver macrophages was determined.

Results. With increasing antibody density, both immunoliposome types showed increased binding to target cells, but type II liposomes displayed better target recognition than type I. Uptake by macrophages increased with antibody density for both liposome types. Lowest uptake by macrophages was found for type II liposomes at low antibody densities. Unexpectedly, not only for type I but also for type II liposomes, in which the antibody is coupled via its Fc moiety, uptake by macrophages was inhibited by aggregated IgG, indicating involvement of Fc receptors. Also polyinosinic acid, an inhibitor of scavenger receptors, reduced uptake of type II liposomes.

Conclusion. Although distal end coupling of antibodies to bilayer-anchored PEG chains in liposomes through the Fc moiety enhances target cell binding, it does not prevent the recognition by Fc receptors on macrophages.

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Authors and Affiliations

  1. Department of Cell Biology, Section Liposome Research, Groningen University Institute for Drug Exploration (GUIDE), Faculty of Medical Sciences, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Gerben A. Koning, Henriëtte W. M. Morselt, Gerrit L. Scherphof & Jan A. A. M. Kamps

  2. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O Box 80 082, 3508 TB, Utrecht, The Netherlands

    Gerben A. Koning

  3. Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Arko Gorter

  4. Department of Pharmacology, University of Alberta, Edmonton, Canada, T6G 2H7

    Theresa M. Allen

  5. ALZA Corporation, Palo Alto, California, 94303-0802, USA

    Samuel Zalipsky

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  1. Gerben A. Koning
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  2. Henriëtte W. M. Morselt
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  3. Arko Gorter
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  4. Theresa M. Allen
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  5. Samuel Zalipsky
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  6. Gerrit L. Scherphof
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  7. Jan A. A. M. Kamps
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Correspondence to Jan A. A. M. Kamps.

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Koning, G.A., Morselt, H.W.M., Gorter, A. et al. Interaction of Differently Designed Immunoliposomes with Colon Cancer Cells and Kupffer Cells. An in Vitro Comparison. Pharm Res 20, 1249–1257 (2003). https://doi.org/10.1023/A:1025009300562

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  • DOI: https://doi.org/10.1023/A:1025009300562

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