A tiny nanoparticle one-thousandth the width of a human hair could someday shield war fighters against potential chemical and biological warfare.
Researchers from Sandia National Laboratories created the particle, known as the “protocell,” as a drug-delivery system to boost the effectiveness of disease-fighting therapies. It’s already being adapted for use against some cancers in partnership with the University of New Mexico.
Now, the U.S. Department of Defense wants the lab to develop it into an antibiotic delivery system to create an effective vaccine against chemical and biological weapons. The DOD’s Defense Threat Reduction Agency has approved a four-year, $10.8 million grant to fund the project, which will begin with laboratory tests on rats at UNM, followed by additional tests in about two years at Lovelace Respiratory Research Institute.
The goal is to use protocells to encapsulate and deliver antibiotics to treat infections caused by two types of bacteria in particular – Francisella tularensis and Burkholderia pseudomallei – said Carlee Ashley, a chemical engineer and principal investigator on the project. Both of those bacteria have been used in weapons in the past.
“The DOD and the Centers for Disease Control are very concerned about them because they’re highly infectious,” Ashley said. “It only takes between 10 and 50 particles of bacteria exposure to cause full-blown disease. They’re very nasty bacteria.”
Protocells are particularly promising as an antibiotic delivery system because the nanoparticles are engineered to specifically target infected tissue, reducing the possibility of side effects, said Eric Carnes, another Sandia chemical engineer and researcher on the project. In fact, the antibiotics would remain imprisoned in the protocells unless bacteria get into the body.
“They’re engineered to activate if there is bacteria; otherwise, they will just be excreted from the body,” Carnes said.
Research on the project also could help lay the foundation for using protocells to deliver many other antibiotics and anti-viral drugs in the future.
“It’s a platform that can be used to treat multiple bio-weapons and conditions,” Ashley said. “The DOD is basically funding us to develop flexible materials that can easily be adapted for whatever new bio or chemical threat arises.”
Indeed, the protocell was built as a “platform technology,” or a broad-based invention that can be used in many different applications, said Jeff Brinker, a Sandia researcher and UNM professor who has directed work on the protocell for more than a decade at Sandia’s Advanced Materials Center and at UNM’s Biomedical Engineering Center.
“The original concept was to create a particle capable of delivering any drug to any target cell,” Brinker said. “We can load the particle up with anti-cancer drugs, or with drugs for chemical and bio-defense. It’s a universal platform to deliver therapeutic cargos.”
The protocell consists of a porous nanoparticle made of silica material that easily dissolves in the body. The particle is chock full of holes, or tubes, which can carry a range of drugs, including multiple medicines at the same time.
The exterior of the protocell is covered with a protective coating similar to the membranes that surround cells, plus a protein that allows them to bind with targeted tissue, such as cancer cells.
The membrane coating seals the drugs inside the protocell. And because the coating is biologically compatible with human tissue, the nanoparticle can float harmlessly in the bloodstream until it binds with targeted cells to release their cargoes inside the diseased tissue.
The concept of using nanoparticles to deliver drugs to targeted cells emerged 10 to 15 years ago and is now being widely researched at universities and laboratories nationwide.
But Sandia’s protocell has proved more robust and effective than other nanoparticles, with less possibility of breaking down in the bloodstream and much greater ability to target specific cells, Brinker said. Moreover, unlike most nanoparticles, which are engineered to target one type of molecule with just one drug, the protocell can be adapted to target different types of cells with a multitude of drugs.
Brinker and his lab teams developed the protocell with about $3 million in funding from both the U.S. Department of Energy and internal Sandia financing. Brinker is now working with UNM medical researchers to apply the protocell as an anti-cancer therapy with about $3.75 million from the National Cancer Institute and the Leukemia and Lymphoma Society. Private investors also have stepped in to help commercialize it.
In addition, over the past three years, Sandia has spent about $3 million of its own funds to develop defense applications for the protocell, helping pave the way for the new DOD grant. And the lab recently earmarked another $1.25 million to engineer the protocell for fighting antibiotic-resistant bacteria.