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Nanoscale Bacteria Particles Deliver Cancer Drugs

Salmonella typhimurium

Salmonella typhimurium bacteria (Volker Brinkmann, Wikimedia Commons)

21 Dec. 2018. An engineering lab developed techniques for delivering cancer drugs into tumors in lab cultures and mice with nanoscale polymer particles, aided by a strain of salmonella bacteria. The technology developed at Virginia Polytechnic Institute and State University, or Virginia Tech, in Blacksburg is described in the 5 December issue of the journal Advanced Science.

A team from the lab of mechanical engineering professor Bahareh Behkam, with colleagues from other Virginia Tech engineering and life science departments, is seeking better methods to deliver cancer treatments directly into solid tumors. Systemic treatments like chemotherapy often produce serious adverse effects in cancer patients, and while nanoscale particles of these drugs can concentrate in tumors, say the researchers, it’s often difficult to deliver these nanoparticles through the bloodstream and across tumor tissue in sufficient quantities to be effective.

Behkam and colleagues aimed at building on recent findings showing the ability of some bacteria strains to seek out and penetrate tumor cells. This ability of bacteria to penetrate tumor tissue has been known for centuries. However, some of those bacterial strains, such as Salmonella, are associated with food poisoning and other serious diseases, requiring changes in the bacteria genomes to remove or at least minimize the potential for disease if used to treat cancer.

One Salmonella strain, Typhimurium VNP20009, shows particular promise as a cancer-targeting bacteria, by its affinity for tumor tissue and cells. The Virginia Tech team developed a process for weakening the bacteria, to retain the ability to find cancerous tumors on their own when injected into the blood stream, but not cause infections like those encountered from food poisoning. The researchers also load up the bacteria with nanoscale particles carrying an anti-cancer agent. The nanoparticles are made from poly lactic-co-glycolic acid, or PLGA, a common, biocompatible polymer used for time-released drug delivery.

“Its (salmonella’s) job as a pathogen is to penetrate through the tissue,” says Behkam in a Virginia Tech statement. “What we thought is if bacteria are so good at moving through the tissue, how about coupling nanomedicine with the bacterium to carry that medicine much farther than it’d passively diffuse on its own?”

The researchers call this technology nanoscale bacteria-enabled autonomous drug delivery system, or NanoBeads. They first tested NanoBeads in lab cultures with tumor samples of brain, colon, and breast cancer cells from humans and mice. These tests not only show the ability of NanoBeads to penetrate the tumors, they enabled the researchers to better understand the mechanism for NanoBeads activity in the tumors, as well as devise methods for measuring NanoBeads’ activity inside the tumors. The team found NanoBeads accumulate 80 times more in the tumors than polymer nanoparticles on their own.

The team then tested NanoBeads on lab mice induced with breast cancer. The NanoBeads in this case were coated with streptavidin, a protein with anti-cancer toxicity, but usually not able to penetrate tumors on their own. The researchers found NanoBeads, injected into the blood streams of the mice, accumulated 100-fold in the tumors, compared to the liver, without any external force such as a magnetic field to direct the particles to the tumors.

The researchers plan to continue collaborations with engineering, life science, medical, and veterinary medicine departments at Virginia Tech to advance the technology beyond this proof-of-concept into more animal tests and eventually clinical trials.

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