Scientists are investigating a way to use temporary tattoos that deliver nanoparticles to treat autoimmune diseases like multiple sclerosis.
“Placed just under the skin, the carbon-based particles form a dark spot that fades over about one week as they are slowly released into the circulation,” says Christine Beeton, a scientist at Baylor College of Medicine.
The tiny particles, modified with polyethylene glycol, are conveniently choosy as they are taken up by cells in the immune system.
“We can inject into an area that’s hidden, or use micropattern needles and shape it.”
T and B lymphocyte cells and macrophages are key components of the immune system. However, in many autoimmune diseases such as multiple sclerosis, T cells are the key players. One suspected cause is that T cells lose their ability to distinguish between invaders and healthy tissue and attack both.
In tests at Baylor, nanoparticles were internalized by T cells, which inhibited their function, but ignored by macrophages.
“The ability to selectively inhibit one type of cell over others in the same environment may help doctors gain more control over autoimmune diseases,” says Beeton.
“The majority of current treatments are general, broad-spectrum immunosuppressants,” says Redwan Huq, lead author of the Nature study and a graduate student in the Beeton lab. “They’re going to affect all of these cells, but patients are exposed to side effects (ranging) from infections to increased chances of developing cancer.
“So we get excited when we see something new that could potentially enable selectivity.”
‘It was completely unexpected’
Since the macrophages and other splenic immune cells are unaffected, most of a patient’s existing immune system remains intact, he adds.
The soluble nanoparticles synthesized by the Rice University lab of chemist James Tour have shown no signs of acute toxicity in prior rodent studies, Huq says. They combine polyethylene glycol with hydrophilic carbon clusters, hence their name, PEG-HCCs.
The carbon clusters are 35 nanometers long, 3 nanometers wide and an atom thick, and bulk up to about 100 nanometers in globular form with the addition of PEG. They have proven to be efficient scavengers of reactive oxygen species called superoxide molecules, which are expressed by cells the immune system uses to kill invading microorganisms.
T cells use superoxide in a signaling step to become activated. PEG-HCCs remove this superoxide from the T cells, preventing their activation without killing the cells.
Beeton became aware of PEG-HCCs during a presentation by former Baylor graduate student Taeko Inoue, a coauthor of the new study.
“As she talked, I was thinking, ‘That has to work in models of multiple sclerosis,'” Beeton says. “I didn’t have a good scientific rationale, but I asked for a small sample of PEG-HCCs to see if they affected immune cells.”
“We found they affected the T lymphocytes and not the other splenic immune cells, like the macrophages. It was completely unexpected,” she says.
The Baylor lab’s tests on animal models showed that small amounts of PEG-HCCs injected under the skin are slowly taken up by T lymphocytes, where they collect and inhibit the cell’s function. They also found the nanoparticles did not remain in T cells and dispersed within days after uptake by the cells.
“That’s an issue because you want a drug that’s in the system long enough to be effective, but not so long that, if you have a problem, you can’t remove it,” Beeton says. “PEG-HCCs can be administered for slow release and don’t stay in the system for long. This gives us much better control over the circulating half-life.”
“The more we study the abilities of these nanoparticles, the more surprised we are at how useful they could be for medical applications,” Tour says.
Hide it or shape it
Beeton suggests delivering carbon nanoparticles just under the skin rather than into the bloodstream would keep them in the system longer, making them more available for uptake by T cells. And the one drawback—a temporary but visible spot on the skin that looks like a tattoo—could actually be a perk to some.
“We saw it made a black mark when we injected it, and at first we thought that’s going to be a real problem if we ever take it into the clinic,” Beeton says. “But we can work around that. We can inject into an area that’s hidden, or use micropattern needles and shape it.
The Baylor College of Medicine, the National Multiple Sclerosis Society, National Institutes of Health, the Dan L. Duncan Cancer Center, John S. Dunn Gulf Coast Consortium for Chemical Genomics, and the US Army-funded Traumatic Brain Injury Consortium provided support.
Source: Rice University