A bacterial protein enhances the release and efficacy of liposomal cancer drugs.
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.
Cheong
Ian
I
Howard Hughes Medical Institute and the Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
Huang
Xin
X
Bettegowda
Chetan
C
Diaz
Luis A
LA
Kinzler
Kenneth W
KW
Zhou
Shibin
S
Vogelstein
Bert
B
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003013:Clostridium / Q000737:chemistry* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D006801:Humans; D000077146:Irinotecan; D008049:Lipase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009368:Neoplasm Transplantation; D017434:Protein Structure, Tertiary
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D000077146:Irinotecan; D004317:Doxorubicin; D008049:Lipase; C547320:liposomase, Clostridium novyi; D002166:Camptothecin