Scientists use modified salmonella to smuggle cancer-fighting particles into the tumor
Coming up with potent anti-cancer drugs is one thing, delivering them to the site of a tumor inside the body is very much another. With a complicated organism guarded by a highly evolved immune system to navigate, getting these particles to there target in one piece is a challenging task, and one that scientists are continuing to tackle from all angles. A promising new approach developed at Virginia Tech leans on the penetrative properties of a salmonella infection, which they've found can be used as a vehicle to smuggle cancer-fighting nanoparticles into a tumor in a huge abundance.
This new technique stems from how the body responds to foreign cells that present it with a threat, like those carried by salmonella and other types of infections. When confronted with this bacteria, the body's immune system swings into action to fight it, which can spell bad news for the cancer cells caught in the cross fire. This forms part of the field of immunotherapy, where scientists are exploring ways to supercharge the body's immune system to overpower cancer, and making advances all the time.
The Virgina Tech team wondered if, as well as triggering the body's immune system, the salmonella bacteria could also be augmented to carry anti-cancer drugs to the site of a tumor with greater effectiveness. This idea first occurred to Virginia Tech mechanical engineer Bahareh Behkam six years ago, so it hasn't exactly been a short path to success, but after lots of tinkering she and her team have now produced some hugely promising results.
They have dubbed the technology Bacteria-Enabled Autonomous Drug Delivery System, or NanoBEADS. It consists of nanoparticles made from poly(lactic‐co‐glycolic acid) to carry anti-cancer drugs, chemically attached to an attenuated bacteria strain Salmonella enterica serovar Typhimurium VNP20009.
This is a weakened version of salmonella made to still provoke an immune reaction, but without the harmful effects a salmonella infection can carry. It was also chosen as it has been vigorously studied in a phase one clinical trial.
"Salmonella's job as a pathogen is to penetrate through the tissue," Behkam said. "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 team explored the penetrative abilities of the NanoBEADS by putting them to work in lab-grown tumors, where they found up to an 80-fold improvement in nanoparticle penetration and distribution, compared to conventionally diffused nanoparticles. Not content with that, the researchers administered the NanoBEADs to mice with breast cancer, and found that they vastly improved the retention of nanoparticles within solid tumors by up to 100 times, compared to passive delivery methods.
"Most notably, the salmonella itself helped keep the particles in the tumor up to 100-fold better, which would suggest it would be an effective delivery vehicle," said study co-author Coy Allen.
From here, the team is looking to actually load up the NanoBEADS with cancer therapeutics to see how it can impact their effectiveness.
"You can make the most amazing drugs, but if you cannot deliver it where it needs to go, it cannot be very effective," Behkam said. "By improving the delivery, you can enhance efficacy."
The team's research has been published in the journal Advanced Science.
Source: Virginia Tech