Cancer drug delivery made possible by “masked” bacteria
Researchers have developed a cloaking system that temporarily hides therapeutic bacteria from immune detection, in cancer-ridden mouse models. Professors of engineering at Columbia University School of Engineering and Applied Science (Columbia Engineering), programmed gene circuits to build a protective molecular “cloak” around bacteria – this ingenious system opens up a new drug delivery strategy specifically for metastasised and distal tumours.
According to data, the ideal bacteria should be able to evade the immune system as it makes its way to the tumour. Once the job is done, the bacteria must also be safely eliminated in other parts of the body to minimise toxicity.
[Despite their intended use for drug delivery, bacteria are nevertheless alive and can proliferate within the body. They are detected by the body’s immune systems as foreign and dangerous, causing high inflammatory response – too much bacteria translates to high toxicity while too little bacteria means no therapeutic efficacy.]
Columbia Engineering researchers focused on capsular polysaccharides (CAP) which are sugar polymers that coat bacterial surfaces to engineer a new system was called inducible CAP, or iCAP. In nature, CAP helps many bacteria to protect themselves from attacks including immune systems.
iCAP then allows for “programmable and dynamic alteration of the bacterial cell surface” using a small molecule known as IPTG. iCAP enabled the researchers to control the time to which bacteria can survive in human blood, in this case by tuning how much IPTG they give to the iCAP E. coli.
However, when the researchers did not give IPTG to the animal subjects, the E. coli iCAP was noted to lose its encapsulation over time and was easier to be eliminated in other parts of the body, thus minimising toxicity.
Additionally, the iCAP system was able to control both tumour growth and bacterial leakage in the animal models. Past studies have shown that low levels of bacteria leak out from tumours upon tumour growth. But with iCAP the researchers demonstrated controllable bacterial migration within the body – they injected E. coli iCAP into one tumour, fed the mice with water containing IPTG, activated iCAP within the tumour, and saw E. coli iCAP leak out and migrate to uninjected tumours.
Kam Leong, Columbia’s Samuel H. Sheng Professor of Biomedical Engineering, said, “Bacterial cancer therapy holds unique advantages over conventional drug therapy, such as efficient targeting of the tumour tissue and programmable drug release. Potential toxicity has been limiting its full potential. The cloaking approach presented in this study may address this critical issue.”
Read: Cancer drug delivery made more potent with microbubbles
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