Immunoliposomes bearing polyethyleneglycol-coupled Fab' fragment show prolonged circulation time and high extravasation into targeted solid tumors in vivo

FEBS Lett. 1997 Aug 11;413(1):177-80. doi: 10.1016/s0014-5793(97)00905-8.

Abstract

We have developed a new type of long-circulating immunoliposome (Fab'-PEG immunoliposomes) which is efficiently extravasated into the targeted solid tumor in vivo. Small unilamellar liposomes (100-130 nm in diameter) were prepared from distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and a dipalmitoylphosphatidylethanolamine derivative of PEG with a terminal maleimidyl group (DPPE-PEG-Mal), and conjugated Fab' fragment of antibody. Inclusion of DPPE-PEG-Mal and linkage of the Fab' fragment instead of intact antibody to PEG terminals allowed the liposomes to evade RES uptake and remain in the circulation for a long time, resulting in enhanced accumulation of the liposomes in the solid tumor. Because of the ability of such Fab'-PEG immunoliposomes to target solid tumors, they appear highly attractive as carriers of not only chemotherapeutic agents, but also of macromolecular drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoembryonic Antigen / immunology
  • Cholesterol / chemistry
  • Cholesterol / metabolism
  • Extravasation of Diagnostic and Therapeutic Materials
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / metabolism
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Liposomes / immunology
  • Liposomes / metabolism
  • Liposomes / therapeutic use*
  • Liver / metabolism
  • Maleimides / chemistry
  • Maleimides / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neoplasms, Experimental
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / metabolism
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / metabolism
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / metabolism
  • Polyethylene Glycols / therapeutic use
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / therapy*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Carcinoembryonic Antigen
  • Immunoglobulin Fab Fragments
  • Liposomes
  • Maleimides
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • maleimide
  • 1,2-dipalmitoyl-3-phosphatidylethanolamine
  • Polyethylene Glycols
  • Cholesterol
  • 1,2-distearoyllecithin