Cancer-curing radioisotopes are attracted by engineered microorganisms to tumours.


Cancer-killing radioisotopes are attracted into Tumour by Engineered bacteria

Targeting multiple tumour types Nalinikanth Kotagiri and colleagues have developed a new type of targeted radionuclide therapy
(Courtesy: Colleen Kelley/University of Cincinnati)

An emerging cancer treatment therapy named Targeted radionuclide therapy (TRT) in which radiopharmaceuticals travel through the bloodstream and selectively bind to cancer cells. Once they enter inside the tumour, the radionuclides emit alpha or beta particles, sending their energy into a local area and killing the surrounding cancer cells. 

The effectiveness of current TRT strategies depends on the presence of distinct receptors that the radiopharmaceutical  can bind to on the surface of cancer cells. Because of this targeting, the medicine only affects the cancer cells, sparing normal tissue and organs. Effective targeting strategies can be developed, although tumour heterogeneity and cell mutation can change the receptor profile.

In order to overcome this difficulty, scientists at the University of Cincinnati are creating a brand-new TRT delivery Strategy  that could target and eliminate various cancer types, regardless of their receptor profile. They demonstrate how tumour-colonizing bacteria can draw a bacteria-specific radiopharmaceutical into cancer cells, even those without receptors to target, in a proof-of-concept study published in Advanced Healthcare Materials.

A metal absorption receptor was overexpressed on the surface of the probiotic Escherichia coli Nissle (EcN) by senior author Nalinikanth Kotagiri and collaborators through genetic engineering. A bacteria-specific radiopharmaceutical  containing yersiniabactin (YbT), a siderophore molecule that binds to metals, is then used to attract the modified bacteria, which can be injected into solid tumours. YbT is marked with the therapeutic radioisotope 67Cu.

Kotagiri said in a press release that the radioactive metal will be transported as long as the modified bacteria are present inside a tumour. If a cancer cell is expressing a receptor or not, they won't give a damn. They are just concerned with having found something they can recognize, gather, and hold onto.

Furthermore, by switching out 67Cu for 64Cu, which can be seen via PET, the location of the bacteria inside the tumour may be tracked. When imaging a tumor, Kotagiri says, "We can seamlessly switch between copper-64 and copper-67, and then once we've imaged, we can introduce another molecule again to do therapy."

Bacterial encroachment:

The buildup of the modified EcN in vivo was initially examined by the researchers using PET/CT. They gave 64Cu-YbT after directly injecting the bacteria into the tumours caused by colon cancer in rats. While PET/CT showed noticeably larger signals in tumours carrying modified EcN compared to a bacteria strain that does not express the metal absorption receptor, bioluminescence imaging validated bacterial localization in the tumour. They point out that the liver and kidneys were principally responsible for clearing the 64Cu-YbT probe, with just minor buildup in other important organs.

Bacterial localization Bioluminescence (left) and PET/CT (right) images demonstrate the presence of engineered EcN in colon cancer tumours 18 days after intratumoural injection.
Bacterial localization Bioluminescence (left) and PET/CT (right) images demonstrate the presence of engineered EcN in colon cancer tumours 18 days after intratumoural injection. (Courtesy: N A Siddiqui et al Adv. Healthcare Mater. 10.1002/adhm.202202870)

Only the tumours were significantly contaminated with bacteria one and seven days after injection, according to an examination of the excised organs. All main organs had bacterial levels below the threshold for detection. Two days after giving the bacteria to a different set of mice, the researchers found that there were roughly 10 times as many germs in the tumours as there had been 48 hours earlier.

The modified bacteria not only maintained their population inside solid tumours on day 18, when the cancer was already quite large, but also attained continuous development that was compatible with the growth of the tumour itself, according to both bioluminescence Imaging and PET/CT.

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