An interdisciplinary team of three Virginia Tech faculty members affiliated with the Macromolecules Innovation Institute has created a drug delivery system that could radically expand cancer treatment options.
The conventional cancer treatment method of injecting nanoparticle drugs into the bloodstream results in low efficacy. Due to the complexities of the human body, very few of those nanoparticles actually reach the cancer site, and once there, there’s limited delivery across the cancer tissue.
The new system created at Virginia Tech is known as Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS). Researchers have developed a process to chemically attach nanoparticles of anti-cancer drugs onto attenuated bacteria cells, which they have shown to be more effective than the passive delivery of injections at reaching cancer sites.
NanoBEADS has produced results in both in vitro (in tumor spheroids) and in vivo (in living mice) models showing up to 100-fold improvements in the distribution and retention of nanoparticles in cancerous tissues.
This is a product of the five-year National Science Foundation CAREER Award of Bahareh Behkam, associate professor of mechanical engineering. Collaborators on this interdisciplinary team are Rick Davis, professor of chemical engineering, and Coy Allen, assistant professor of biomedical sciences and pathobiology in the Virginia-Maryland College of Veterinary Medicine.
“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.”
This work, which combines expertise in mechanical engineering, biomedical engineering, chemical engineering, and veterinary medicine, was recently detailed in Advanced Science.
Using salmonella for good
Humans have noticed, even as far back as Ancient Egypt, that cancer went into remission if the patient also contracted an infection like salmonella. Neither are ideal, but humans can treat salmonella infections more effectively than cancer.
In modern times, Allen said the idea of treating cancer with infections traces back to the late 1800s and has evolved into immunotherapy, in which doctors try to activate the immune system to attack cancerous cells.
Of course, salmonella is harmful to humans, but a weakened version could in theory provide the benefits of immunotherapy without the harmful effects of salmonella infection. The concept is similar to humans receiving a weakened flu virus in a vaccine to build immunity.
Over six years ago, Behkam came up with the idea of augmenting bacterial immunotherapy to also attack cancer with conventional anti-cancer drugs. The problem was the passive delivery of anti-cancer drugs doesn’t work very well.
Given her background in bio-hybrid microrobotics, she wanted to use salmonella bacteria as autonomous vehicles to transport the medicine, in nanoparticle form, directly to the cancer site.
The work began with Behkam’s first doctoral student, Mahama Aziz Traore, constructing the first generation of NanoBEADS by assembling tens of polystyrene nanoparticles onto E. coli bacteria. After thoroughly studying the dynamics and control aspects of the NanoBEADS systems for a few years, Behkam brought Davis into the project because he had experience creating polymer nanoparticles for drug delivery.
“She mentioned this radically different approach for delivering drugs and nanoparticles,” Davis said. “I walked away from the conversation thinking, ‘Man, if this thing could work, it would be fantastic.’”
Behkam chose this particular bacterial strain, Salmonella enterica serovar Typhimurium VNP20009, because it has been thoroughly studied and successfully tested in a phase one clinical trial.
“Its (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?”