A bacterial protein enhances the release and efficacy of liposomal cancer drugs

Science. 2006 Nov 24;314(5803):1308-11. doi: 10.1126/science.1130651.

Abstract

Clostridium novyi-NT is an anaerobic bacterium that can infect hypoxic regions within experimental tumors. Because C. novyi-NT lyses red blood cells, we hypothesized that its membrane-disrupting properties could be exploited to enhance the release of liposome-encapsulated drugs within tumors. Here, we show that treatment of mice bearing large, established tumors with C. novyi-NT plus a single dose of liposomal doxorubicin often led to eradication of the tumors. The bacterial factor responsible for the enhanced drug release was identified as a previously unrecognized protein termed liposomase. This protein could potentially be incorporated into diverse experimental approaches for the specific delivery of chemotherapeutic agents to tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacokinetics
  • Camptothecin / therapeutic use
  • Cell Line, Tumor
  • Cloning, Molecular
  • Clostridium / chemistry*
  • Clostridium / genetics
  • Colorectal Neoplasms / drug therapy*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Drug Carriers
  • Humans
  • Irinotecan
  • Lipase / chemistry
  • Lipase / genetics
  • Lipase / metabolism*
  • Lipid Bilayers / chemistry
  • Liposomes / chemistry
  • Liposomes / metabolism*
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Transplantation
  • Protein Structure, Tertiary

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • Drug Carriers
  • Lipid Bilayers
  • Liposomes
  • Irinotecan
  • Doxorubicin
  • Lipase
  • liposomase, Clostridium novyi
  • Camptothecin