In Situ Delivery of Biobutyrate by Probiotic Escherichia Coli for Cancer Therapy

Overview

Journal Sci Rep

Specialty Science

Date 2021 Sep 14

PMID 34518590

Citations 14

Authors

Chung-Jen Chiang

Yan-Hong Hong

Affiliations

Soon will be listed here.

Abstract

Butyrate has a bioactive function to reduce carcinogenesis. To achieve targeted cancer therapy, this study developed bacterial cancer therapy (BCT) with butyrate as a payload. By metabolic engineering, Escherichia coli Nissle 1917 (EcN) was reprogrammed to synthesize butyrate (referred to as biobutyrate) and designated EcN-BUT. The adopted strategy includes construction of a synthetic pathway for biobutyrate and the rational design of central metabolism to increase the production of biobutyrate at the expense of acetate. With glucose, EcN-BUT produced primarily biobutyrate under the hypoxic condition. Furthermore, human colorectal cancer cell was administrated with the produced biobutyrate. It caused the cell cycle arrest at the G1 phase and induced the mitochondrial apoptosis pathway independent of p53. In the tumor-bearing mice, the injected EcN-BUT exhibited tumor-specific colonization and significantly reduced the tumor volume by 70%. Overall, this study opens a new avenue for BCT based on biobutyrate.

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References

Jiang S, Phan T, Nam T, Nguyen V, Kim H, Bom H . Inhibition of tumor growth and metastasis by a combination of Escherichia coli-mediated cytolytic therapy and radiotherapy. Mol Ther. 2010; 18(3):635-42. PMC: 2839435. DOI: 10.1038/mt.2009.295. View

Tredan O, Galmarini C, Patel K, Tannock I . Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst. 2007; 99(19):1441-54. DOI: 10.1093/jnci/djm135. View

He B, Sui X, Yu B, Wang S, Shen Y, Cong H . Recent advances in drug delivery systems for enhancing drug penetration into tumors. Drug Deliv. 2020; 27(1):1474-1490. PMC: 7594734. DOI: 10.1080/10717544.2020.1831106. View

Baudino T . Targeted Cancer Therapy: The Next Generation of Cancer Treatment. Curr Drug Discov Technol. 2015; 12(1):3-20. DOI: 10.2174/1570163812666150602144310. View

Tannock I, Lee C, Tunggal J, Cowan D, Egorin M . Limited penetration of anticancer drugs through tumor tissue: a potential cause of resistance of solid tumors to chemotherapy. Clin Cancer Res. 2002; 8(3):878-84. View

Navya P, Kaphle A, Srinivas S, Bhargava S, Rotello V, Daima H . Current trends and challenges in cancer management and therapy using designer nanomaterials. Nano Converg. 2019; 6(1):23. PMC: 6626766. DOI: 10.1186/s40580-019-0193-2. View

Yazawa K, Fujimori M, Nakamura T, Sasaki T, Amano J, Kano Y . Bifidobacterium longum as a delivery system for gene therapy of chemically induced rat mammary tumors. Breast Cancer Res Treat. 2001; 66(2):165-70. DOI: 10.1023/a:1010644217648. View

Malmgren R, FLANIGAN C . Localization of the vegetative form of Clostridium tetani in mouse tumors following intravenous spore administration. Cancer Res. 1955; 15(7):473-8. View

Forbes N, Munn L, Fukumura D, Jain R . Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors. Cancer Res. 2003; 63(17):5188-93. View

10.

Min J, Nguyen V, Kim H, Hong Y, Choy H . Quantitative bioluminescence imaging of tumor-targeting bacteria in living animals. Nat Protoc. 2008; 3(4):629-36. DOI: 10.1038/nprot.2008.32. View

11.

Leschner S, Westphal K, Dietrich N, Viegas N, Jablonska J, Lyszkiewicz M . Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha. PLoS One. 2009; 4(8):e6692. PMC: 2724709. DOI: 10.1371/journal.pone.0006692. View

12.

Kasinskas R, Forbes N . Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res. 2007; 67(7):3201-9. DOI: 10.1158/0008-5472.CAN-06-2618. View

13.

Van Dessel N, Swofford C, Forbes N . Potent and tumor specific: arming bacteria with therapeutic proteins. Ther Deliv. 2015; 6(3):385-99. PMC: 4423202. DOI: 10.4155/tde.14.113. View

14.

Sznol M, Lin S, Bermudes D, Zheng L, King I . Use of preferentially replicating bacteria for the treatment of cancer. J Clin Invest. 2000; 105(8):1027-30. PMC: 300839. DOI: 10.1172/JCI9818. View

15.

NAUTS H, SWIFT W, COLEY B . The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M.D., reviewed in the light of modern research. Cancer Res. 2010; 6:205-16. View

16.

Hosseinidoust Z, Mostaghaci B, Yasa O, Park B, Singh A, Sitti M . Bioengineered and biohybrid bacteria-based systems for drug delivery. Adv Drug Deliv Rev. 2016; 106(Pt A):27-44. DOI: 10.1016/j.addr.2016.09.007. View

17.

Lehouritis P, Springer C, Tangney M . Bacterial-directed enzyme prodrug therapy. J Control Release. 2013; 170(1):120-31. DOI: 10.1016/j.jconrel.2013.05.005. View

18.

Xiang S, Fruehauf J, Li C . Short hairpin RNA-expressing bacteria elicit RNA interference in mammals. Nat Biotechnol. 2006; 24(6):697-702. DOI: 10.1038/nbt1211. View

19.

Kim J, Phan T, Nguyen V, Dinh-Vu H, Zheng J, Yun M . Salmonella typhimurium Suppresses Tumor Growth via the Pro-Inflammatory Cytokine Interleukin-1β. Theranostics. 2015; 5(12):1328-42. PMC: 4615736. DOI: 10.7150/thno.11432. View

20.

Fensterle J, Bergmann B, Yone C, Hotz C, Meyer S, Spreng S . Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B. Cancer Gene Ther. 2007; 15(2):85-93. DOI: 10.1038/sj.cgt.7701109. View