A Bacterial Protein Enhances the Release and Efficacy of Liposomal Cancer Drugs

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Abstract
Clostridium novyi-NTis an anaerobic bacterium that can infect hypoxic regions within experimental tumors. BecauseC. novyi-NTlyses 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 withC. novyi-NTplus 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.