A bacterial protein enhances the release and efficacy of liposomal cancer drugs

被引:141
作者
Cheong, Ian
Huang, Xin
Bettegowda, Chetan
Diaz, Luis A., Jr.
Kinzler, Kenneth W.
Zhou, Shibin [1 ]
Vogelstein, Bert
机构
[1] Johns Hopkins Kimmel Comprehens Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA
[2] Johns Hopkins Kimmel Comprehens Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA
关键词
D O I
10.1126/science.1130651
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1308 / 1311
页数:4
相关论文
共 18 条
[1]   Bacteriolytic therapy can generate a potent immune response against experimental tumors [J].
Agrawal, N ;
Bettegowda, C ;
Cheong, I ;
Geschwind, JF ;
Drake, CG ;
Hipkiss, EL ;
Tatsumi, M ;
Dang, LH ;
Diaz, LA ;
Pomper, M ;
Abusedera, M ;
Wahl, RL ;
Kinzler, KW ;
Zhou, SB ;
Huso, DL ;
Vogelstein, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (42) :15172-15177
[2]   The use of clostridial spores for cancer treatment [J].
Barbe, S. ;
Van Mellaert, L. ;
Anne, J. .
JOURNAL OF APPLIED MICROBIOLOGY, 2006, 101 (03) :571-578
[3]  
BETTEGWODA C, IN PRESS NAT BIOTECH
[4]   Combination bacteriolytic therapy for the treatment of experimental tumors [J].
Dang, LH ;
Bettegowda, C ;
Huso, DL ;
Kinzler, KW ;
Vogelstein, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (26) :15155-15160
[5]  
Drummond DC, 1999, PHARMACOL REV, V51, P691
[6]  
Fang J, 2003, ADV EXP MED BIOL, V519, P29
[7]   Cancer therapy with radiolabeled and drug/toxin-conjugated antibodies [J].
Govindan, SV ;
Griffiths, GL ;
Hansen, HJ ;
Horak, ID ;
Goldenberg, DM .
TECHNOLOGY IN CANCER RESEARCH & TREATMENT, 2005, 4 (04) :375-391
[8]   Openings between defective endothelial cells explain tumor vessel leakiness [J].
Hashizume, H ;
Baluk, P ;
Morikawa, S ;
McLean, JW ;
Thurston, G ;
Roberge, S ;
Jain, RK ;
McDonald, DM .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (04) :1363-1380
[9]   Bacterial biocatalysts: Molecular biology, three-dimensional structures, and biotechnological applications of lipases [J].
Jaeger, KE ;
Dijkstra, BW ;
Reetz, MT .
ANNUAL REVIEW OF MICROBIOLOGY, 1999, 53 :315-+
[10]   Lessons from phase III clinical trials on anti-VEGF therapy for cancer [J].
Jain, RK ;
Duda, DG ;
Clark, JW ;
Loeffler, JS .
NATURE CLINICAL PRACTICE ONCOLOGY, 2006, 3 (01) :24-40