Genetically engineered bacteria deliver chemotherapy directly to tumors

Traditional chemotherapy often poses significant challenges, including severe side effects, damage to healthy tissue, and limited effectiveness.

Now, researchers from 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 required dose of drugs to treat cancer.

Led by Associate Professor Matthew Chang, researchers from NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) and Synthetic Biology Translational Program (Syn Bio TRP) at NUS Medicine have identified a new drug delivery method that offers hope of developing new clinical treatments for patients with cancer. The results, published in Nature Communications, demonstrate a new method of delivering chemotherapy drugs directly to tumor sites using natural interactions between bacteria and cancer cells.

Propharmacology involves the use of inactive molecules (prodrugs) that are transformed into active drugs within the body, especially in tumor environments, due to the unique conditions of tumors, such as low oxygen levels or high acidity, to activate the drug directly at the site of the cancer, minimizing damage healthy tissues. However, current prodrug strategies have limited target specificity and often rely on macromolecular carriers, which complicates both drug distribution and clearance.

To overcome these limitations, researchers at NUS Medicine have developed a prodrug delivery method that uses a commensal Lactobacillus strain that specifically binds to cancer cells through 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 tumor site.

In preclinical models of nasopharyngeal cancer, genetically modified bacteria localized directly to the tumor and released a 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, since the strain of Lactobacillus identified by the researchers specifically binds to cancer cells.

Lead researcher Dr Shen Haosheng, a postdoctoral fellow at SynCTI, said: "By exploiting the affinity between bacteria and cancer cells, we aim to revolutionize chemotherapy delivery. We are assessing the binding affinity of multiple microbial strains to different cancer cell lines with the aim of developing a universal delivery system using microbial strains to target chemotherapy drugs to various mucosal cancers such as colorectal, urinary, gastric, oral, lung and nasal cancers."

"Cancer treatment is often an extremely difficult experience for patients. Our research represents a significant step towards developing a more targeted and less toxic approach to fighting cancer. We hope 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.