Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems

Joanna Ewa Adrian, Klaas Poelstra, Gerrit Scherphof, Ingrid Molema, D.K F Meijer, Catharina Reker-Smit, Henriette Morselt, Jan Kamps

Research output: Contribution to journalArticleAcademicpeer-review

44 Citations (Scopus)

Abstract

Background/Aims: In designing a versatile liposomal drug carrier to hepatic stellate cells (HSC), the interaction of mannose 6-phosphate human serum albumin (M6P-HSA) liposomes with cultured cells was studied.

Methods: M6P-HSA was covalently coupled to the liposomal surface and the uptake and binding of 3H-labelled M6P-HSA liposomes by primary rat HSC and liver endothelial cells was determined. The targeting ability of M6P-HSA liposomes to HSC was tested in bile duct ligated rats using immunohistochemical methods.

Results: The association of M6P-HSA liposomes with HSC was 4-fold higher than of control liposomes. An excess of M6P-HSA inhibited this association by 58%, indicating M6P receptor specificity. The scavenger receptor competitor polyinosinic acid abolished association of M6P-HSA liposomes with HSC. M6P-HSA liposomes also amply associated with endothelial cells, which abundantly express scavenger receptors. Endocytosis of M6P-HSA liposomes by HSC was temperature dependent and could be inhibited by monensin. In the fibrotic liver M6P-HSA liposomes co-localised with HSC.

Conclusions: Coupling of M6P-HSA to liposomes strongly increases the in vitro uptake of these liposomes by HSC and endothelial cells. Both the mannose 6-phosphate receptor and the scavenger receptors are involved in the uptake process. M6P-HSA liposomes are potential drug carriers to HSC in the fibrotic liver. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)560-567
Number of pages8
JournalJournal of Hepatology
Volume44
Issue number3
DOIs
Publication statusPublished - Mar-2006

Keywords

  • hepatic stellate cells
  • liposomes
  • M6P/IGF II receptor
  • liver fibrosis
  • scavenger receptor
  • GROWTH-FACTOR-BETA
  • MANNOSE 6-PHOSPHATE
  • SCAVENGER RECEPTOR
  • ENDOTHELIAL-CELLS
  • II RECEPTOR
  • IN-VIVO
  • RAT
  • ACTIVATION
  • ALBUMIN
  • LIVER

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