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

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.
Authors	Ian Cheong, Xin Huang, Chetan Bettegowda, Luis A Diaz Jr, Kenneth W Kinzler, Shibin Zhou, Bert Vogelstein
Journal	Science (New York, N.Y.) (Science) Vol. 314 Issue 5803 Pg. 1308-11 (Nov 24 2006) ISSN: 1095-9203 [Electronic] United States
PMID	17124324 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Bacterial Proteins Drug Carriers Lipid Bilayers Liposomes Irinotecan Doxorubicin Lipase liposomase, Clostridium novyi Camptothecin
Topics	Amino Acid Sequence Animals Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use) Bacterial Proteins (chemistry, genetics, metabolism) Base Sequence Camptothecin (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use) Cell Line, Tumor Cloning, Molecular Clostridium (chemistry, genetics) Colorectal Neoplasms (drug therapy) Doxorubicin (administration & dosage, pharmacokinetics, therapeutic use) Drug Carriers Humans Irinotecan Lipase (chemistry, genetics, metabolism) Lipid Bilayers (chemistry) Liposomes (chemistry, metabolism) Mice Molecular Sequence Data Mutation Neoplasm Transplantation Protein Structure, Tertiary

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