Possibility of the reversal of multidrug resistance and the avoidance of side effects by liposomes modified with MRK-16, a monoclonal antibody to P-glycoprotein

Hirotami Matsuo, Masahiro Wakasugi, Hitomi Takanaga, Hisakazu Ohtani, Mikihiko Naito, Takashi Tsuruo, Yasufumi Sawada

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

For cancer chemotherapy, avoiding the side effects of chemotherapeutic agents is difficult. Multidrug resistance is one of the major obstacles to successful cancer chemotherapy. P-Glycoprotein (P-gp) serves as an efflux pump and plays a key role in the multidrug resistance. We examined the effect of MRK-16, a monoclonal antibody against P-gp, modified liposomes (MRK-Lip) on the human myelogenous leukemia K-562 cells and its adriamycin resistance cell line K-562/ADM cells to avoid the side effects and to reverse the multidrug resistance. The uptake of vincristine (VCR) by K-562/ADM cells was lower than that by K-562 cells. This low uptake was increased in the presence of verapamil and MRK-16, however, it was not increased in the presence of control antibody, IgG2A. The binding of MRK-Lip to K-562/ADM cells was higher than that of IgG2A-modified liposome (IgG-Lip) and liposome without modification (Cont-Lip). Moreover, the cytotoxicity of VCR-encapsulated MRK-Lip to K-562/ADM cells was higher than that of VCR-encapsulated IgG-Lip and Cont-Lip. These results suggest that the interaction between liposomes and multidrug resistance cells was increased by the modification of liposomes with MRK-16. Consequently, the usefulness of MRK-Lip in cancer chemotherapy as a potent carrier was suggested.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalJournal of Controlled Release
Volume77
Issue number1-2
DOIs
Publication statusPublished - 2001 Nov 9
Externally publishedYes

Keywords

  • Cancer chemotherapy
  • Liposome
  • Multidrug resistance
  • P-Glycoprotein
  • Side effect

ASJC Scopus subject areas

  • Pharmaceutical Science

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