Aptamers Applied in Bacterial-Mediated Biotherapy

While bacterial-mediated biotherapy has been extensively studied for treating various cancers, its practical application remains limited due to insufficient therapeutic efficacy. This is primarily because, after administration, the bacteria cannot accumulate at effective concentrations within the tumor.

This study describes a method that significantly promotes the localization of bacteria to tumor sites after systemic administration. This is achieved by conjugating aptamers to the bacterial surface via a simple and cytocompatible amidation procedure. This preparation has minimal impact on bacterial activity, with aptamer-modified bacteria (ApCB) showing growth similar to unmodified bacteria. The grafting density of aptamers on the bacterial surface can be easily adjusted by controlling the feeding ratio, ranging from 0.7×10^5 to 5.7×10^5 aptamers per bacterium. More importantly, this conjugation prevents enzymatic hydrolysis of surface-bound aptamers; studies showed that up to 80% of aptamers remained intact after 24 hours of exposure to serum. Furthermore, with 2.8×10^5 aptamers per bacterium, the ApCB exhibited the highest specificity for tumor cells in in vitro tests and achieved 2-fold and 4-fold greater tumor tissue accumulation at 12 hours and 60 hours, respectively, after intravenous injection in mice, compared to unmodified bacteria.

This study demonstrates a strategy for modulating bacterial targeting through simple surface modification. By conjugating aptamers to the attenuated Salmonella Typhimurium VNP20009 (VNP) strain, the ApCB showed significantly enhanced immune responses and anti-tumor efficacy in 4T1 and H22 tumor mouse models, further highlighting the promise of ApCB in enhancing bacterial-mediated cancer therapy.

Reference：

https://pubmed.ncbi.nlm.nih.gov/34782610/