Silver nanoparticles help fight brain-eating amoebas
This is one in a series presenting news on technology and innovation, made possible with generous support from the Lemelson Foundation.
Brain-eating amoebas are the stuff of nightmares. People infected with these microscopic monsters typically die within a week. To treat infections, doctors currently use a chemical cocktail of drugs. Even with treatment, however, these parasites usually prove fatal. But that may change. In fact, a new silver “bullet” might — quite literally — prove their downfall.
Researchers in Malaysia report that silver nanoparticles can make drugs more effective as they fight off brain-eating amoebas. The scientists began by growing two kinds of these parasites in test tubes. Both have unruly names. One is Acanthamoeba castellanii (Ah-KAN-thuh-MEE-buh Kas-tel-LAHN-ee-eye). The other is Naegleria fowleri (NAYG-lehr-ee-uh Fow-LAER-ee). The researchers treated these amoebas with drugs. Some got only the drugs. Others got the drugs together with a dose of silver nanoparticles. The silver greatly boosted the killing power of most drugs, the new study reports.
Marion Paolini is a cancer scientist working at the Massachusetts Institute of Technology in Cambridge. Although not involved in the new work, she does find the new treatment “promising.” However, she notes “it would still have to be proven in vivo.” By that, she means it needs to be tested in people or some other animal, not just in the test tube.
The new research was published October 15 in ACS Chemical Neuroscience.
What inspired the new treatment
Brain-eating amoebas are rare. Only a few hundred infections have ever been reported. But the outcome for people who do become infected is grim. About 98 out of every 100 infected people die. Sometimes, the amoebas literally eat away parts of their brains. Other times, the microbes cause a fatal swelling in the brain.
Ayaz Anwar is a biologist at Sunway University in Sunway City, Malaysia. He became interested in these microscopic parasites after one of his relatives died from an amoebic infection.
“We don't know what can kill the infection,” Anwar says. Currently, doctors prescribe a mix of several different drugs. This includes drugs that kill cancer cells and fungi. It’s unclear which of those drugs have helped the few people who have survived, he says.
These drugs typically are injected into the blood. From there, they move throughout the body. Yet few of them can pass from the blood into the brain, where the infection can hide. Anwar’s team decided to use a drug that could pass from the blood to the brain. Anti-seizure drugs do this. Some scientists had suspected these drugs might be effective against amoebas. An added benefit, Anwar notes: These anti-seizure drugs are known to be safe.
To test the drugs’ amoeba-killing power, the Sunway team grew amoebas in test tubes and counted them. Then they treated the parasites with one of three drugs: valium, luminal or dilantin. Each of these anti-seizure drugs fought both amoeba species — killing some, but not all of them.
Anwar thought they could do better.
Their second innovation
“Only a little amount of a drug can reach the target,” he notes. Free-floating drugs often get lost, especially in the human body. So he enlisted the use of nanoparticles to work “like a courier service.” Basically, they help carry more of the drug to the brain infection.
Silver nanoparticles are about a millionth the size of a baseball. Drugs stick to these tiny silver balls, like noodles around a meatball. This prevents the drugs from floating away before they reach the amoebas. Silver itself can also kill cells. Anwar suspected that by combining it with the seizure meds, the duo might prove a double whammy against the single-celled parasites.
And his team’s new data suggest he was right.
They tested each of the three drugs alone and again with the nanosilver. That silver boosted the ability of the seizure drugs to kill amoebas. Against A. castellani, the silver more than tripled each drug’s ability to kill amoebas. It didn’t work quite as well against N. fowleri. Those nanoparticles boosted the amoeba-killing value of only valium and luminal.
Previous work by Anwar’s team had hinted that nanosilver might help other drugs fight amoebas. The new tactic — pairing them with anti-seizure drugs — appears to show real promise. Still, the new treatment is a long way from being ready for use in people. But Anwar already has a plan for how to apply the silver nanoparticles and drugs. He wants to spray them up your nose.
“These amoebas enter the brain through the easiest route,” he says. That often is up through the nose. Earlier this year, a news report described a woman who died from brain-eating amoebas. The source? She had rinsed out her nose with water that later turned out to be infected.
“What we propose is that we can also follow the same track of the amoebas,” says Anwar. Doctors can deliver the drug as a nasal spray.
But Paolini has a word of caution.
“Silver nanoparticles' advantages are also their drawbacks: They can be toxic, and can kill bacteria and tumor cells,” she says. So, she warns, “Without proper targeting, they can also be toxic to healthy cells.”
That’s why the next step by Anwar’s team is testing the new therapy in mice. That can serve as a first test of the combo’s safety.
amoeba A single-celled microbe that catches food and moves about by extending fingerlike projections of a colorless material called protoplasm. Amoebas are either free-living in damp environments or they are parasites.
bacteria (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals).
biology The study of living things. The scientists who study them are known as biologists.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
innovation (v. to innovate; adj. innovative) An adaptation or improvement to an existing idea, process or product that is new, clever, more effective or more practical.
literally A term that the phrase that it modifies is precisely true. For instance, to say: "It's so cold that I'm literally dying," means that this person actually expects to soon be dead, the result of getting too cold.
microscopic An adjective for things too small to be seen by the unaided eye. It takes a microscope to view objects this small, such as bacteria or other one-celled organisms.
Naegleria fowleri A single-celled freshwater parasite, sometimes called the “brain-eating amoeba.” It lives in hot springs and other surface waters that get very warm.
nanoparticle A small particle with dimensions measured in billionths of a meter.
nasal Having to do with the nose.
neuroscience The field of science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.
parasite An organism that gets benefits from another species, called a host, but doesn’t provide that host any benefits. Classic examples of parasites include ticks, fleas and tapeworms.
seizure A sudden surge of electrical activity within the brain. Seizures are often a symptom of epilepsy and may cause dramatic muscle spasms.
species A group of similar organisms capable of producing offspring that can survive and reproduce.
tactic An action or plan of action to accomplish a particular feat.
technology The application of scientific knowledge for practical purposes, especially in industry — or the devices, processes and systems that result from those efforts.
therapy (adj. therapeutic) Treatment intended to relieve or heal a disorder.
toxic Poisonous or able to harm or kill cells, tissues or whole organisms. The measure of risk posed by such a poison is its toxicity.
tumor A mass of cells characterized by atypical and often uncontrolled growth. Benign tumors will not spread; they just grow and cause problems if they press against or tighten around healthy tissue. Malignant tumors will ultimately shed cells that can seed the body with new tumors. Malignant tumors are also known as cancers.
Journal: A. Anwar et al. Clinically-approved drugs against CNS diseases as potential therapeutic agents to target brain-eating amoebae. ACS Chemical Neuroscience. Published online October 15, 2018. doi: 10.1021/acschemneuro.8b00484.
News report: H. Rodriguez. Rare brain-eating amoebas killed Seattle woman who rinsed her sinuses with tap water. Doctor warns this could happen again. The Seattle Times. December 6, 2018.