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Genetically engineered bacteria deliver chemotherapy directly to tumors
Last reviewed: 02.07.2025
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Traditional chemotherapy often has significant challenges, including severe side effects, damage to healthy tissue, and limited effectiveness.
Now, researchers at the National University of Singapore's Yong Loo Lin School of Medicine (NUS Medicine) have developed a revolutionary approach to cancer treatment - a more targeted, effective and less toxic alternative to traditional chemotherapy. This new approach not only improves the effectiveness of treatment, but also significantly reduces the dose of drugs needed to treat cancer.
Led by Associate Professor Matthew Chang, researchers from NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) and the Synthetic Biology Translational Programme (Syn Bio TRP) at NUS Medicine have identified a new drug delivery method that offers hope for developing new clinical treatments for cancer patients. The findings, published in the journal Nature Communications, demonstrate a new method for delivering chemotherapy drugs directly to tumour sites, using natural interactions between bacteria and cancer cells.
Prodrugs involve the use of inactive molecules (prodrugs) that are transformed into active drugs within the body, particularly in tumor environments, using the unique conditions of tumors, such as low oxygen or high acidity, to activate the drug directly at the site of cancer while minimizing damage to healthy tissue. However, current prodrug strategies have limited target specificity and often rely on macromolecular carriers, complicating both drug distribution and elimination.
To overcome these limitations, researchers at NUS Medicine have developed a prodrug delivery method that uses a commensal strain of Lactobacillus that specifically binds to cancer cells via a surface molecule called heparan sulfate. These genetically modified bacteria carry a prodrug that is converted into the chemotherapy drug SN-38 directly at the tumour site.
In preclinical models of nasopharyngeal cancer, genetically modified bacteria localized directly to the tumor and released the chemotherapy drug directly at the cancer site, reducing tumor growth by 67% and increasing the effectiveness of the chemotherapy drug by 54%.
One of the most promising aspects of this research is the potential broad applications for various types of cancer therapy, as the Lactobacillus strain identified by the researchers specifically binds to cancer cells.
Lead researcher Dr Shen Haosheng, a research fellow at SynCTI, said: "By exploiting the affinity between bacteria and cancer cells, we aim to revolutionise chemotherapy delivery. We are evaluating the binding affinity of multiple microbial strains to different cancer cell lines with the aim of developing a versatile delivery system that uses microbial strains to target chemotherapeutic drugs to different mucosal cancers such as colorectal, urinary, gastric, oral, lung and nasal cancers."
"Cancer treatment is often an extremely difficult ordeal for patients. Our research represents a significant step towards developing a more targeted and less toxic approach to fighting cancer. We hope that this can pave the way for therapies that are both gentle and effective," added Associate Professor Chang, Chair of the Department of Medicine and Director of SynCTI and NUS Medicine Syn Bio TRP.