[P005] Poster

12:10 PM - 1:00 PM JST(3:10 AM - 4:00 AM UTC)

[P03-309] Prodrug-conjugated tumour-seeking commensals for targeted cancer therapy

Haosheng Shen^1,2,3, Changyu Zhang^4,5, Shengjie Li^1,6, Yuanmei Liang^1,2,3,7, ○Li Ting Lee^1,2,3, Nikhil Aggarwal^1,2,3, Kwok Soon Wun^1,2,3,7, Jing Liu⁸, Saravanan Prabhu Nadarajan^1,2,7, Cheng Weng⁵, Hua Ling^1,2,7,11, Joshua K. Tay^1,2,9, De Yun Wang⁸, Shao Q. Yao⁵, In Young Hwang^1,2,12, Yung Seng Lee^1,2,10, Matthew Wook Chang^1,2,3,7 (1. NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore (Singapore), 2. Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore (Singapore), 3. National Centre for Engineering Biology (NCEB) (Singapore), 4. Ningbo Institute of Dalian University of Technology (China), 5. Department of Chemistry, National University of Singapore (Singapore), 6. Institute of Translational Medicine, Jiangxi Medical College, Nanchang University (China), 7. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (Singapore), 8. Department of Otolaryngology, Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (Singapore), 9. Department of Otolaryngology-Head and Neck Surgery, National University of Singapore (Singapore), 10. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore (Singapore), 11. Present address: Wilmar International Limited (Singapore), 12. Present address: Food, Chemical and Biotechnology, Singapore Institute of Technology (Singapore))

Keywords:

Prodrug,Bacteria-mediated cancer therapy,Commensals,Lactobacillus,Nasopharyngeal carcinoma

Conventional chemotherapy is limited by systemic toxicity, poor bioavailability, and low tumour specificity. Prodrugs improve selectivity through activation by tumour microenvironment (TME) cues, but their delivery remains imprecise. Here, we develop a bacteria-based delivery platform that harnesses tumour–microbiome interactions for targeted prodrug delivery. Using nasopharyngeal carcinoma (NPC) as a model, we identify Lactobacillus plantarum WCFS1 as a commensal strain with high-affinity binding to NPC cells. We engineer this strain to display streptavidin on its surface, enabling high-capacity loading of biotinylated prodrugs. A thioketal linker responsive to TME cues was conjugated to SN-38, a chemotherapeutic compound, to enable controlled drug release in the TME. Prodrug-loaded bacteria selectively bind NPC cells and locally release active SN-38, increasing cytotoxic potency up to 10-fold in vitro. In a C666-1 xenograft mouse model, systemic administration of prodrug-loaded bacteria resulted in tumour colonisation and significant tumour growth inhibition (67%) at reduced dosing, without observable toxicity. This work establishes a living, tumour-targeting delivery system that enables modular and site-specific activation of chemotherapeutics, with potential applications across diverse cancer types.