Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes

Int J Pharm. 2007 Sep 5;342(1-2):194-200. doi: 10.1016/j.ijpharm.2007.04.037. Epub 2007 May 10.


Immunoliposomes are potent carriers for targeting of therapeutic drugs to specific cells. Membrane type-1 matrix metalloproteinase (MT1-MMP), which plays an important role in angiogenesis, is expressed on angiogenic endothelium cells as well as tumor cells. Then, the MT1-MMP might be useful as a target molecule for tumor and neovascularity. In the present study, we addressed a utility of antibodies against the MT1-MMP as a targeting ligand of liposomal anticancer drug. Fab' fragments of antibody against the MT1-MMP were modified at distal end of polyethylene glycol (PEG) of doxorubicin (DXR)-encapsulating liposomes, DXR-sterically stabilized immunoliposomes (DXR-SIL[anti-MT1-MMP(Fab')]). Modification with the antibody significantly enhanced cellular uptake of DXR-SIL[anti-MT1-MMP(Fab')] into the HT1080 cells, which highly express MT1-MMP, compared with the non-targeted liposomes (DXR-stealthliposomes (DXR-SL)), suggesting that MT1-MMP antibody (Fab') is a potent targeting ligand for the MT1-MMP expressed cells. In vivo systemic administration of DXR-SIL[anti-MT1-MMP(Fab')] into the tumor-bearing mice showed significant suppression of tumor growth compared to DXR-SL. This is presumably due to the active targeting of immunoliposomes for tumor and neovascularity. However, tumor accumulation of DXR-SIL[anti-MT1-MMP(Fab')] and DXR-SL were comparable, suggesting that both liposomal formulations accumulated in tumor via enhanced permeation and retention (EPR) effect, but not via targeting to the MT1-MMP expressed on both the endothelial and tumor cells. It appears that the enhanced antitumor activity of DXR-SIL[anti-MT1-MMP(Fab')] resulted from acceleration of cellular uptake of lioposomes owing to the incorporated antibody after extravasation from capillaries in tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use*
  • Drug Compounding
  • Drug Delivery Systems
  • Excipients
  • Immunochemistry
  • Immunoglobulin Fab Fragments / chemistry
  • Liposomes
  • Male
  • Matrix Metalloproteinase 14 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Polyethylene Glycols / chemistry


  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal
  • Excipients
  • Immunoglobulin Fab Fragments
  • Liposomes
  • Polyethylene Glycols
  • Doxorubicin
  • Matrix Metalloproteinase 14