Tumor-targeting prodrug-activating bacteria for cancer therapy

doi:10.1038/cgt.2008.10

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 藥學系(所) > 期刊論文 > Item 310902800/21735

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標題:	Tumor-targeting prodrug-activating bacteria for cancer therapy
作者:	C-M Cheng Y-L Lu K-H Chuang W-C Hung J Shiea Y-C Su C-H Kao B-M Chen S Roffler T-L Cheng
貢獻者:	藥學系
關鍵字:	non-invasive imaging b-glucuronidase glucuronide prodrug optical imaging luminescence prodrug-activating bacteria
日期:	2008-03
上傳時間:	2009-10-13 10:52:55 (UTC+8)
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. -glucuronidase and the luxCDABE gene cluster were expressed in the DH5 strain of Escherichia coli to generate DH5-lux/G. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase I inhibitor 9-aminocamptothecin (9AC). By optical imaging, colony-forming units (CFUs) and staining for G activity, we found that DH5-lux/G preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and G activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5-lux/G, 9AC or 9ACG treatment, combined systemic administration of DH5-lux/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.
關聯:	Cancer Gene Therapy 15：p.393-401
顯示於類別:	[藥學系(所)] 期刊論文

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