Patients of the future might find doctors injecting tiny bits of silica into their brains. Tomas Guilarte wants to find out whether that’s safe.
His preliminary answer, based on experiments with lab rats: Maybe yes, maybe no.
Researchers are experimenting with different kinds of nanoparticles – ranging in size from one-billionth of a meter to perhaps 100 times that – for help in scanning and treating brain tumors.
At that size, some materials can bypass the blood-brain barrier, which normally protects the brains from toxins in the bloodstream. The hope is that nanomedicines will make it easier to diagnose tumors and even deliver drugs directly into the out-of-control cells.
Silica is considered one of the safest potential nano-vehicles, especially compared to toxic metals such as mercury and cadmium. But nanosilica might also harm the brain, says Guilarte, a neurotoxicologist at Columbia University.
In his experiments – the first of their kind—Guilarte found that nanosilica made its way into the rat brains’ immune defender cells, known as microglia.
On the one hand, the silica didn’t kill the cells or interfere with their ability to do one of their primary jobs – gobbling up other invaders. That’s good news.
On the other hand, the nanosilica caused changes that could lead to inflammation and other injury to the brain – bad news, if further studies bear it out.
“All Bets Are Off”
Guilarte presented his findings on April 29 at John Hopkins University in Baltimore, where he was on the faculty until recently. The university’s Institute for NanoBio Technology, or INBT, held a symposium on the health and environmental effects of engineered nanomaterials.
That’s a mouthful. Nanotechnology is the science of creating and manipulating substances at the scale of the nanometer, or a billionth of a meter. Nanosized stuff occurs in nature and by accident. Sometimes it’s harmless. Sometimes – as with the so-called “ultrafine” particles in welding fumes and diesel exhaust – it is toxic. Only in recent decades have scientists and manufacturers learned how to produce nanomaterials on purpose. Those are the engineered nanomaterials that INBT is concerned about.
The magic of nanotechnology is that it defies many of the usual laws of chemistry and physics. Ordinary substances like carbon and silver, whose normal behavior is well-understood, act differently when shrunk to the scale of atoms and molecules.
That unpredictability means they can do wondrous things. In the world of consumer products, nanomaterials contribute to super-strong, super-light sporting goods; to clothes that repel stains and wrinkles; to mold-fighting paints and kitchenwares.
But the novelty has a downside. Many at the Johns Hopkins symposium were scientists working in the burgeoning field of nanomedicine, trying to develop treatments for diseases from cancer to cystic fibrosis. One of the institute’s co-founders, professor Jonathan Links, warned them that the same unpredictable properties that give promise to their lab experiments also mean “that all bets are off when it comes to the risks.”
First Line Of Defense
Primary rat microglia in culture.
Guilarte focused on the potential hazards of nanosilica to the microglia precisely because other researchers are focusing on the potential benefits.
Brain tumors are notoriously hard to get at — not only because they are surrounded by the skull and precious brain tissue, but also because the body does a great job of protecting the brain against intruders, including tumor-shrinking drugs.
Microglia, the cells Guilarte studied, are the first line of defense.
“Microglia are the cell type in the brain that are constantly surveying the environment,” he explained at the symposium. They make up about 10 percent of the brain cell population. And “any intrusion, they respond within seconds.”
After extracting microglia from newborn rat brains, Guilarte and colleagues exposed them to varying concentrations of silica nanoparticles. They found that the microglia took in the nanoparticles at all concentrations.
The brain cells survived just fine, and they maintained their ability to swallow up invaders – in this case, tiny plastic beads – an immune system process known as phagocytosis.
However, the microglia showed other signs of possible injury. They produced high levels of molecules known as reactive oxygen species and reactive nitrogen species, which together can cause cell damage. Also, after exposure to the nanosilica, the microglia’s levels of a tumor-killing gene dropped sharply. At the same time, they showed significant increases in a gene that promotes inflammation and is often linked with cancer.
Guilarte’s study, published this month in the journal Environmental Health Perspectives, emphasizes that more research is needed. The next step is to expose microglia to nanosilica not in a test tube, but in the brain of a living animal. Also, Guilarte’s team looked at effects only 24 hours after exposure. What happens later: Do the brain cells get rid of the offending nanoparticles? Or does the damage worsen?
Between Guilarte and the rats, a lot of brains are working on these questions. Let’s hope they find some answers soon.