A bacterial protein enhances the release and efficacy of liposomal cancer drugs |
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Authors: | Cheong Ian Huang Xin Bettegowda Chetan Diaz Luis A Kinzler Kenneth W Zhou Shibin Vogelstein Bert |
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Institution: | Howard Hughes Medical Institute and the Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA. |
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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. |
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