Researchers Develop Less Toxic, More Effective Chemotherapy

Researchers at NUS Medicine have modified the bacteria to deliver targeted chemotherapy.

Traditional chemotherapy frequently comes with major problems, including harsh side effects, damage to healthy cells, and limited efficacy.

Researchers at the National University of Singapore Yong Loo Lin School of Medicine (NUS Medicine) have developed a groundbreaking cancer treatment. This new technology is a more precise, effective and less harmful alternative to traditional chemotherapy. Not only does it improve the efficacy of treatment, it also significantly reduces the dosage of drugs needed to treat cancer.

Researchers from the NUS Clinical Technology Innovation Synthetic Biology (SynCTI) and NUS Medicine’s Synthetic Biology Translational Programme (Syn Bio TRP), led by Associate Professor Matthew Chan, have identified a new drug delivery method that offers hope for the development of new clinical treatments for cancer patients. Nature CommunicationsWe present a new method that exploits the natural interaction between bacteria and cancer cells to deliver chemotherapy drugs directly to tumor sites.

Prodrug strategies and bacterial innovation

Prodrugs are inactive molecules that are converted into active drugs in the body, particularly in the tumor environment, and take advantage of tumor-specific conditions such as hypoxia and high acidity to activate drugs precisely at the cancer site and minimize damage to healthy tissue. However, current prodrug strategies have limited target specificity and often rely on polymeric carriers, complicating both drug distribution and clearance.

To overcome these limitations, researchers at NUS Medicine have developed a prodrug delivery method using symbiotic organisms. Lactic acid bacteria strain that specifically binds to cancer cells via a surface molecule called heparan sulfate. These engineered bacteria carry a prodrug that converts to the chemotherapy drug SN-38 at the tumor site. In a preclinical model of nasopharyngeal carcinoma, the engineered bacteria specifically localized to tumors and released the chemotherapy drug directly to the cancer site, inhibiting tumor growth by 67% and increasing the efficacy of the chemotherapy drug by 54%.

Potential for broader application in cancer treatment

One of the most promising aspects of this research is its potential broad application in treating different types of cancer. Lactic acid bacteria The strains the researchers identified bind specifically to cancer cells. Dr. Shen Haosheng, a research scientist at SynCTI and lead investigator, said: “By harnessing the affinity between bacteria and cancer cells, we aim to revolutionize chemotherapy delivery. We are evaluating the binding affinity of multiple microbial strains to multiple cancer cell lines, aiming to develop a versatile delivery system that uses microbial strains to target chemotherapy drugs to various mucosal cancers, including colorectal, bladder, gastric, oral, lung and nasal cancers.”

“Cancer treatments often take a huge toll on patients. Our research is a major step towards developing a more targeted, less toxic approach to fighting cancer. We hope this will pave the way for gentler, more effective treatments,” added Associate Professor Chan, Dean of the School of Medicine and director of SynCTI and NUS Medicine Syn Bio TRP.

Reference: “Prodrug-Conjugated Tumor-Seeking Probiotics for Targeted Cancer Therapy” Haosheng Shen, Changyu Zhang, Shengjie Li, Yuanmei Liang, Li Ting Lee, Nikhil Aggarwal, Kwok Soon Wun, Jing Liu, Saravanan Prabhu Nadarajan, Cheng Weng, Hua Ling, Joshua K. Tay, De Yun Wang, Shao Q. Yao, In Young Hwang, Yung Seng Lee, Matthew Wook Chang, May 21, 2024, Nature Communications.
DOI: 10.1038/s41467-024-48661-y