Tumor-targeting prodrug-activating bacteria for cancer therapy

被引：70

作者：

Cheng, C-M ^{[6
]}

Lu, Y-L ^{[3
]}

Chuang, K-H ^{[6
]}

Hung, W-C ^{[2
,4
]}

Shiea, J. ^{[4
,5
]}

Su, Y-C ^{[1
]}

Kao, C-H ^{[6
]}

Chen, B-M ^{[7
]}

Roffler, S. ^{[7
]}

Cheng, T-L ^{[1
,4
]}

机构：

[1] Kaohsiung Med Univ, Fac Biomed & Environm Biol, Sch Biomed Sci & Environm Biol, Kaohsiung 80708, Taiwan

[2] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan

[3] Chia Nan Univ Pharm & Sci, Tainan, Taiwan

[4] Natl Sun Yat Sen Univ, Kaohsiung Med Univ, Joint Res Ctr, Kaohsiung, Taiwan

[5] Natl Sun Yat Sen Univ, Dept Chem, Kaohsiung 80424, Taiwan

[6] Kaohsiung Med Univ, Grad Inst Med, Kaohsiung, Taiwan

[7] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

来源：

CANCER GENE THERAPY | 2008年 / 15卷 / 06期

关键词：

non-invasive imaging; beta-glucuronidase; glucuronide prodrug; optical imaging; luminescence; prodrug-activating bacteria;

D O I：

10.1038/cgt.2008.10

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, we developed a strain of bacteria to express enzymes for selective prodrug activation and non-invasive imaging in tumors. beta-glucuronidase and the luxCDABE gene cluster were expressed in the DH5 alpha strain of Escherichia coli to generate DH5 alpha-lux/beta G. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase 1 inhibitor 9-aminocamptothecin ( 9AC). By optical imaging, colony-forming units ( CFUs) and staining for beta G activity, we found that DH5 alpha-lux/beta G preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and beta G activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5 alpha-lux/beta G, 9AC or 9ACG treatment, combined systemic administration of DH5 alpha-lux/beta G followed by 9ACG prodrug treatment significantly ( P<0.005) delayed the growth of CL1-5 tumors. Our results demonstrate that prodrug-activating bacteria may be useful for selective cancer chemotherapy.

引用

页码：393 / 401

页数：9

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