Nanoparticles may have the solution to awful side effects from chemotherapy. If doctors can use nanoparticles to carry drugs directly to a specific part of the body, they can make chemotherapautics less toxic.
But it is not that simple. Because nanoparticles trigger the body’s immune system to fight against them, the vast majority of them never reach their target.
Human blood serum contains proteins that tag the nanoparticles as invadors and a paltry 1% of the nanoparticles get to where they are going.
“No one escapes the wrath of the serum proteins,” said Eden Tanner, who was a postdoctoral Bioengeneering fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).
A research team led by Tanner and Professor Samir Mitragotri have created an ionic forcefield that could enable nanoparticles to achieve their goal by preventing the proteins in the blood serum from tagging the nanoparticles.
In experimenting with mice, the researchers found that the could make the nanoparticles to survive longer in the human body using a coat of the ionic liquid. This coating increased the number of nanoparticles that reached their target from 1% to more than 50%.
“The fact that this coating allows the nanoparticles to slip past serum proteins and hitch a ride on red blood cells is really quite amazing because once you are able to fight the immune system effectively, lots of opportunities open up,” explained Mitragotri, who is part of the Harvard’s Wyss Institute for Biologically Inspired Engineering faculty.
Ionic liquids are liquid salts and they are capable of holding charge.
“We knew that serum proteins clear out nanoparticles in the bloodstream by attaching to the surface of the particle and we knew that certain ionic liquids can either stabilize or destabilize proteins,” said Tanner, an assistant professor of chemistry and biochemistry at the University of Mississippi. “The question was, could we leverage the properties of ionic liquids to allow nanoparticles to slip past proteins unseen.”
The great thing about ionic liquids is that every small change you make to their chemistry results in a big change in their properties,” explained Christine Hamadani, who was the first author and a former graduate student at SEAS. “By changing one carbon bond, you can change whether or not it attracts or repels proteins.”
At the moment, Hamadani is a graduate student based at Tanner’s lab in the University of Mississippi.
Researchers used choline hexenoate to coat the nanoparticles. It is an ionic liquid with a natural aversion to serum proteins. The nanoparticles coated with ionic liquid attached themselves to red-blood cells and remained in circulation until they got to the lungs.
“This hitchhiking phenomenon was a really unexpected discovery,” said Mitragotri. “Previous methods of hitchhiking required special treatment for the nanoparticles to attach to red blood cells and even then, they only stayed at a target location for about six hours. Here, we showed 50 percent of the injected dose still in the lungs after 24 hours.”
The scientists are yet to understand exactly why the nanoparticles so easily attached themselves to lung tissue, but it shows that the system can work with a fair amount of precision.
“This is such a modular technology,” said Tanner, who plans will go on with her research at University of Mississippi. “Any nanoparticle with a surface change can be coated with ionic liquids and there are millions of ionic liquids that can be tuned to have different properties. You could tune the nanoparticle and the liquid to target specific locations in the body.”
“We as a field need as many tools as we can to fight the immune system and get drugs where they need to go,” said Mitragotri. “Ionic liquids are the latest tool on that front.”
Morgan J. Goetz co-authored the research paper.