Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy
Abstract Given the special microenvironment of solid tumors, live microorganisms have emerged as drug delivery vehicles and therapeutic agents. Here, an acid‐induced therapeutic platform is constructed using attenuated Escherichia coli to express the cytolysin A protein. The bacteria can target and...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202105086 |
| _version_ | 1818554691906174976 |
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| author | Wenjun Qin Wenxuan Xu Longyu Wang Debao Ren Yibin Cheng Wen Song Tao Jiang Lixin Ma Cheng Zhang |
| author_facet | Wenjun Qin Wenxuan Xu Longyu Wang Debao Ren Yibin Cheng Wen Song Tao Jiang Lixin Ma Cheng Zhang |
| author_sort | Wenjun Qin |
| collection | DOAJ |
| description | Abstract Given the special microenvironment of solid tumors, live microorganisms have emerged as drug delivery vehicles and therapeutic agents. Here, an acid‐induced therapeutic platform is constructed using attenuated Escherichia coli to express the cytolysin A protein. The bacteria can target and colonize tumor tissues without causing notable host toxicity. Bacterial infection can disrupt blood vessels and trigger thrombosis in tumor tissues, resulting in the cut‐off of nutrient supply to tumor cells and the arrest of tumor growth. The expression of cytolysin A induced by the acidic tumor microenvironment further strengthens thrombosis and provides a complementary therapeutic option due to its pore‐forming function. In a xenograft mouse tumor model, this strategy reduces tumor proliferation by 79% and significantly prevents tumor metastasis, thus paving a new avenue for bacteria‐based tumor therapy. |
| first_indexed | 2024-12-12T09:43:19Z |
| format | Article |
| id | doaj.art-5988eda73bad46799cdf8e6ccda4e747 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-12T09:43:19Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-5988eda73bad46799cdf8e6ccda4e7472022-12-22T00:28:30ZengWileyAdvanced Science2198-38442022-05-01915n/an/a10.1002/advs.202105086Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor TherapyWenjun Qin0Wenxuan Xu1Longyu Wang2Debao Ren3Yibin Cheng4Wen Song5Tao Jiang6Lixin Ma7Cheng Zhang8Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science and Engineering Hubei University Wuhan 430062 P. R. ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering Hubei Key Laboratory of Industrial Biotechnology School of Life Sciences Hubei University Wuhan 430062 P. R. ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering Hubei Key Laboratory of Industrial Biotechnology School of Life Sciences Hubei University Wuhan 430062 P. R. ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering Hubei Key Laboratory of Industrial Biotechnology School of Life Sciences Hubei University Wuhan 430062 P. R. ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering Hubei Key Laboratory of Industrial Biotechnology School of Life Sciences Hubei University Wuhan 430062 P. R. ChinaInstitute of Biology and Medicine & College of Life Science and Health Wuhan University of Science and Technology Wuhan 430081 P. R. ChinaMinistry of Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science and Engineering Hubei University Wuhan 430062 P. R. ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering Hubei Key Laboratory of Industrial Biotechnology School of Life Sciences Hubei University Wuhan 430062 P. R. ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering Hubei Key Laboratory of Industrial Biotechnology School of Life Sciences Hubei University Wuhan 430062 P. R. ChinaAbstract Given the special microenvironment of solid tumors, live microorganisms have emerged as drug delivery vehicles and therapeutic agents. Here, an acid‐induced therapeutic platform is constructed using attenuated Escherichia coli to express the cytolysin A protein. The bacteria can target and colonize tumor tissues without causing notable host toxicity. Bacterial infection can disrupt blood vessels and trigger thrombosis in tumor tissues, resulting in the cut‐off of nutrient supply to tumor cells and the arrest of tumor growth. The expression of cytolysin A induced by the acidic tumor microenvironment further strengthens thrombosis and provides a complementary therapeutic option due to its pore‐forming function. In a xenograft mouse tumor model, this strategy reduces tumor proliferation by 79% and significantly prevents tumor metastasis, thus paving a new avenue for bacteria‐based tumor therapy.https://doi.org/10.1002/advs.202105086acid‐inducedbacterianutrient interruptionthrombosistumor therapy |
| spellingShingle | Wenjun Qin Wenxuan Xu Longyu Wang Debao Ren Yibin Cheng Wen Song Tao Jiang Lixin Ma Cheng Zhang Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy Advanced Science acid‐induced bacteria nutrient interruption thrombosis tumor therapy |
| title | Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy |
| title_full | Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy |
| title_fullStr | Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy |
| title_full_unstemmed | Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy |
| title_short | Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy |
| title_sort | bacteria elicited specific thrombosis utilizing acid induced cytolysin a expression to enable potent tumor therapy |
| topic | acid‐induced bacteria nutrient interruption thrombosis tumor therapy |
| url | https://doi.org/10.1002/advs.202105086 |
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