Application of bacterial directed enzyme prodrug therapy as a targeted chemotherapy approach in a mouse model of breast cancer.
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| Abstract |
Cancer is the second leading cause of death in the world. Some of the usual cancer treatments include surgery, chemotherapy, and radiotherapy. However, due to low efficacy and side effects of these treatments, novel targeted therapeutic methods are needed. One of the common drawbacks of cancer chemotherapy is off-target toxicity. In order to overcome this problem, many investigations have been conducted. One of the new targeted therapy methods known as bacterial directed enzyme-prodrug therapy (BDEPT) employs bacteria as enzyme carriers to convert a pro-drug to a drug specifically within the tumor site. In the present study, we used Escherichia coli DH5α carrying luxCDABE gene cluster and overexpressing β-glucuronidase for luminescent emission and enzyme expression, respectively. Enzyme expression can lead to the conversion of glycyrrhizic acid as a prodrug to glycyrrhetinic acid, a potent anti-cancer agent. DH5α-lux/βG was characterized and its stability was also evaluated. Bacteria colonization in the tumor site was measured by tissue homogenate preparation and colony counting method. Histopathological studies on the liver, spleen, and tumor were also conducted. According to the results, co-treatment of 4T1, a highly metastatic mouse breast cancer cell line, with GL and DH5α-lux/βG could significantly decrease the IC50 values. Moreover, increased number of bacteria could lead to a dramatic drop in IC50 value. Specific colonization of DH5α-lux/βG was observed in the tumor site compared with other tissues (p< 0.0001). Moreover, the biocompatibility evaluation proved that DH5α-lux/βG had no adverse effects on normal tissues. Furthermore, concurrent usage of GL and bacteria in the treatment of induced 4T1 tumors in BALB/c mice significantly delayed tumor growth (p<0.001) during 16 days of investigation. Based on these findings, BDEPT might be useful for targeted breast cancer therapy, although further investigations are required to confirm this.
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| Authors | Niloufar Hosseini-Giv, Ahmad Reza Bahrami, Maryam M Matin |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 606 Pg. 120931 (Sep 05 2021) ISSN: 1873-3476 [Electronic] Netherlands |
| PMID | 34310961 (Publication Type: Journal Article) |
| Copyright | Copyright © 2021 Elsevier B.V. All rights reserved. |
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