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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antineoplastic Agents / administration & dosage*
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Base Sequence
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives
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Camptothecin / pharmacokinetics
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Camptothecin / therapeutic use
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Cell Line, Tumor
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Cloning, Molecular
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Clostridium / chemistry*
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Clostridium / genetics
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Colorectal Neoplasms / drug therapy*
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Doxorubicin / administration & dosage*
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Doxorubicin / pharmacokinetics
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Doxorubicin / therapeutic use
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Drug Carriers
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Humans
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Irinotecan
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Lipase / chemistry
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Lipase / genetics
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Lipase / metabolism*
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Lipid Bilayers / chemistry
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Liposomes / chemistry
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Liposomes / metabolism*
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Mice
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Molecular Sequence Data
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Mutation
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Neoplasm Transplantation
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Protein Structure, Tertiary
Substances
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Antineoplastic Agents
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Bacterial Proteins
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Drug Carriers
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Lipid Bilayers
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Liposomes
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Irinotecan
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Doxorubicin
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Lipase
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liposomase, Clostridium novyi
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Camptothecin