Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 24 November 2006:
Vol. 314. no. 5803, pp. 1308 - 1311
DOI: 10.1126/science.1130651
Prev | Table of Contents | Next

Reports

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

Ian Cheong, Xin Huang, Chetan Bettegowda, Luis A. Diaz, Jr., Kenneth W. Kinzler, Shibin Zhou,* Bert Vogelstein*

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.

The Howard Hughes Medical Institute and the Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.

* To whom correspondence should be addressed. E-mail: sbzhou{at}jhmi.edu (S.Z.); vogelbe{at}jhmi.edu (B.V.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Efficacy of a Genetically-modified Salmonella typhimurium in an Orthotopic Human Pancreatic Cancer in Nude Mice.
C. NAGAKURA, K. HAYASHI, M. ZHAO, K. YAMAUCHI, N. YAMAMOTO, H. TSUCHIYA, K. TOMITA, M. BOUVET, and R. M. HOFFMAN (2009)
Anticancer Res 29, 1873-1878
   Abstract »    Full Text »    PDF »
A Genetically Enhanced Anaerobic Bacterium for Oncopathic Therapy of Pancreatic Cancer.
Z. Li, J. Fallon, J. Mandeli, J. Wetmur, and S. L. C. Woo (2008)
J Natl Cancer Inst 100, 1389-1400
   Abstract »    Full Text »    PDF »
Targeting Cancer with Bugs and Liposomes: Ready, Aim, Fire.
I. Cheong, X. Huang, K. Thornton, L. A. Diaz Jr., and S. Zhou (2007)
Cancer Res. 67, 9605-9608
   Abstract »    Full Text »    PDF »
Drug Resistance and the Solid Tumor Microenvironment.
O. Tredan, C. M. Galmarini, K. Patel, and I. F. Tannock (2007)
J Natl Cancer Inst 99, 1441-1454
   Abstract »    Full Text »    PDF »
Spore Coat Architecture of Clostridium novyi NT Spores.
M. Plomp, J. M. McCaffery, I. Cheong, X. Huang, C. Bettegowda, K. W. Kinzler, S. Zhou, B. Vogelstein, and A. J. Malkin (2007)
J. Bacteriol. 189, 6457-6468
   Abstract »    Full Text »    PDF »
Monotherapy with a tumor-targeting mutant of Salmonella typhimurium cures orthotopic metastatic mouse models of human prostate cancer.
M. Zhao, J. Geller, H. Ma, M. Yang, S. Penman, and R. M. Hoffman (2007)
PNAS 104, 10170-10174
   Abstract »    Full Text »    PDF »
Bugging Tumors to Put Drugs on Target.
R. Juliano (2007)
N. Engl. J. Med. 356, 954-955
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)