Custom Made Smart Particle Could Lead to Better Targeted Therapies

Targeted drug delivery focuses on diseased cells to minimize side effects on normal cells.

Researchers at Stanford University recently redesigned the core of a virus to repurpose its infectious capabilities into a safe mode of delivering vaccines and therapies directly where they are needed.

“We call this a smart particle,” said study lead James Swartz, professor of chemical engineering and of bioengineering at Stanford. “We make it smart by adding molecular tags that act like addresses to send the therapeutic payload where we want it to go.”

Using the smart particle for immunotherapy would involve tagging its outer surface with molecules designed to teach the body’s disease-fighting cells to recognize and destroy cancer, Swartz added.

Researchers are already moving on to the next goal, which is to pack tiny quantities of medicine into the smart particles and deliver them to diseased cells where they will release their payloads.

“This was a proof-of-principle experiment so there’s a lot of work to be done,” Swartz said. “But I believe we can use this smart particle to deliver cancer-fighting immunotherapies that will have minimal side effects.”

Targeted drug delivery is one of the main goals for modern medicine as it focuses remedies on diseased cells to minimize side effects for normal cells, unlike current modes of therapy like chemo and radiation that harm healthy cells in the process of treating cancerous ones.

Many scientists have looked to viruses for the answer to targeted treatments as they have the capability to sneak into cells and release viral payloads. The new paper describes how the researchers designed a virus-like particle that is only a delivery vehicle with no infectious payload.

Researchers began with the hepatitis B virus, which possesses 3 layers. Investigators focused on the non-infectious middle layer called the capsid.

Other researchers had similar ideas regarding the use of hepatitis B virus because its hollow structure is large enough to carry a significant medical payload. In practice, however, the goal seemed unachievable, so when Swartz originally proposed the idea it was shot down.

But Swartz was persistent and eventually found a way to perform this task after several years of research and experimentation. Biotechnologists know how to build the complex protein structures that naturally occur, but the researchers took it a step beyond that.

They didn’t just build the capsid nature provided, but also evaluated the DNA that directs the structure to assemble and re-engineered the code to create a custom-designed capsid that would be invisible to the immune system. It is also sturdy enough to survive travel through the bloodstream and has a surface that would be simple to attach molecular tags to.

Bioengineering the surface was important as well. If researchers wanted the capsid to teach the immune system to destroy cancer cells, for instance, they would hang vaccine tags on the spiky surface.

If they wanted the capsid to deliver medicines, however, they would hang address tags on the spikes. Researchers had to make these modifications without destroying the capability of the capsid’s DNA code to direct 240 copies of 1 protein to self-assemble into a hollow sphere with a spiked surface.

Swartz anticipates the next step to be attaching cancer tags to the surface so the immune system can learn to recognize certain types of cancers. Those experiments will likely occur in mice.

Afterwards, he plans to add an additional function to further engineer the DNA code to make sure the protein can self-assemble in the presence of a small medicinal payload.

Stanford has patented the technology and different aspects are licensed to a biotechnology company. The approach is in its early stages of development and there currently exists no timeframe to indicate when the technology will be in commercial development.

“That will be quite complicated, but we’ve already gotten this far when they said it couldn’t be done,” Swartz said.