Bacteria for transporting cancer drugs| MEDICUS 2024 Issue 3

Bacteria on wheels: A novel platform for transporting cancer drugs

Credit: iStock.com/ koto_feja

Scientists from the Yong Loo Lin School of Medicine at the National University of Singapore, have led the development of a bacteria-based drug-delivery system that has the potential to transform how cancers are treated. The novel system uses bacteria that have an affinity for cancer cells as carriers to deliver drugs precisely to where they are needed—to the heart of cancers. With this approach to cancer treatment delivery, the scientists hope to create a more effective and safer treatment option that also requires smaller doses of drugs.

Traditional chemotherapy can take a heavy toll on patients, study lead investigator Associate Professor Matthew Chang commented: “Our research represents a significant step toward developing a more targeted and less toxic approach to fighting cancer.”

Chang, who is Dean’s Chair Professor at NUS Medicine’s Synthetic Biology Translational Research Programme, led a team that also included scientists from NUS’ Synthetic Biology for Clinical and Technological Innovation, to create bacterial carriers that can efficiently carry drugs in inactivated form, known as prodrugs, to the cancer site, where the specific chemistry of the cancer environment then activates the drug.

“Our research represents a significant step toward developing a more targeted and less toxic approach to fighting cancer.”
Prof Matthew Chang

While prodrugs are being increasingly used to minimise collateral damage to healthy tissue, the use of bacterial carriers in this system will eliminate limitations posed by macromolecular carriers like nanomaterials and antibodies that are routinely used. Their larger size and slow-degrading nature have hindered the complete release of the drugs, and contributed to additional toxic effects in healthy tissues.

There is yet another novel feature to Chang’s drug-delivery system. Current bacteria-mediated cancer therapies in development employ non-native microbes like Salmonella and Listeria that do not show specific binding to cancer cells, and thus may have limited efficacy.

This novel drug-delivery system, instead, uses bacteria that are naturally found in the body and display strong, highly specific binding to cancer cells.

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The binding is mediated through unique molecules on both bacterial and cancer cells that recognise each other in a lock-and-key fashion. In the physiological context, these interactions affect how cancers evolve and respond to treatments. In the novel drug-delivery setting, they play a crucial role in guiding the drug carriers with precision. Once the carriers have docked on the cancer cell, the prodrug which is loaded onto the bacterial surface, is activated to release chemotherapy agents.

Chang’s team tested their approach by using nasopharyngeal cancer cells as the disease model and Lactobacillus plantarum as the bacterial carrier. They found that their method increased the efficacy of the drug by 54 per cent and inhibited cancer growth by as much as 67 per cent.

The team is excited as their findings not only demonstrate that their platform is safe and effective in nasopharyngeal cancers, but also sets the stage for the development of a broad-spectrum therapeutic strategy that will leverage the strong affinity between bacteria and cancer cells.

“We are evaluating the binding affinity of several microbial strains to multiple cancer cell lines with the aim of developing a versatile delivery system using microbial strains to target chemotherapy drugs to various mucosal cancers, such as colorectal, bladder, stomach, oral, lung, and nasal cancer,” added lead researcher Dr Shen Haosheng, who is a research fellow with the programme.

Adapted by Sruthi Jagannathan from NUS News: 2024-06-11_Press-Release_Anti-cancer-drug-carriers.pdf