Nano-antioxidants prove their potential

February 9, 2015
A polyethylene glycol-hydrophilic carbon cluster developed at Rice University has the potential to quench the overexpression of damaging superoxides through the catalytic turnover of reactive oxygen species that can harm biological functions. Credit: Errol Samuel/Rice University

Injectable nanoparticles that could protect an injured person from further damage due to oxidative stress have proven to be astoundingly effective in tests to study their mechanism.

Scientists at Rice University, Baylor College of Medicine and the University of Texas Health Science Center at Houston (UTHealth) Medical School designed methods to validate their 2012 discovery that combined polyethylene glycol-hydrophilic carbon clusters—known as PEG-HCCs—could quickly stem the process of overoxidation that can cause damage in the minutes and hours after an injury.

The tests revealed a single nanoparticle can quickly catalyze the neutralization of thousands of damaging molecules that are overexpressed by the body's cells in response to an injury and turn the molecules into oxygen. These reactive species can damage cells and cause mutations, but PEG-HCCs appear to have an enormous capacity to turn them into less-reactive substances.

The researchers hope an injection of PEG-HCCs as soon as possible after an injury, such as traumatic brain injury or stroke, can mitigate further brain damage by restoring normal oxygen levels to the brain's sensitive circulatory system.

The results were reported today in the Proceedings of the National Academy of Sciences.

"Effectively, they bring the level of reactive oxygen species back to normal almost instantly," said Rice chemist James Tour. "This could be a useful tool for emergency responders who need to quickly stabilize an accident or heart attack victim or to treat soldiers in the field of battle." Tour led the new study with neurologist Thomas Kent of Baylor College of Medicine and biochemist Ah-Lim Tsai of UTHealth.

PEG-HCCs are about 3 nanometers wide and 30 to 40 nanometers long and contain from 2,000 to 5,000 carbon atoms. In tests, an individual PEG-HCC nanoparticle can catalyze the conversion of 20,000 to a million reactive oxygen species molecules per second into molecular oxygen, which damaged tissues need, and hydrogen peroxide while quenching reactive intermediates.

Tour and Kent led the earlier research that determined an infusion of nontoxic PEG-HCCs may quickly stabilize blood flow in the brain and protect against reactive oxygen species molecules overexpressed by cells during a medical trauma, especially when accompanied by massive blood loss.

Their research targeted traumatic brain injuries, after which cells release an excessive amount of the reactive oxygen species known as a superoxide into the blood. These toxic are molecules with one unpaired electron that the immune system uses to kill invading microorganisms. In small concentrations, they contribute to a cell's normal energy regulation. Generally, they are kept in check by superoxide dismutase, an enzyme that neutralizes superoxides.

But even mild traumas can release enough superoxides to overwhelm the brain's natural defenses. In turn, superoxides can form such other reactive as peroxynitrite that cause further damage.

"The current research shows PEG-HCCs work catalytically, extremely rapidly and with an enormous capacity to neutralize thousands upon thousands of the deleterious molecules, particularly superoxide and hydroxyl radicals that destroy normal tissue when left unregulated," Tour said.

"This will be important not only in and stroke treatment, but for many acute injuries of any organ or tissue and in medical procedures such as organ transplantation," he said. "Anytime tissue is stressed and thereby oxygen-starved, superoxide can form to further attack the surrounding good tissue."

The researchers used an electron paramagnetic resonance spectroscopy technique that gets direct structure and rate information for superoxide radicals by counting unpaired electrons in the presence or absence of PEG-HCC antioxidants. Another test with an oxygen-sensing electrode, peroxidase and a red dye confirmed the particles' ability to catalyze superoxide conversion.

"In sharp contrast to the well-known superoxide dismutase, PEG-HCC is not a protein and does not have metal to serve the catalytic role," Tsai said. "The efficient catalytic turnover could be due to its more 'planar,' highly conjugated carbon core."

The tests showed the number of superoxides consumed far surpassed the number of possible PEG-HCC bonding sites. The researchers found the particles have no effect on important nitric oxides that keep blood vessels dilated and aid neurotransmission and cell protection, nor was the efficiency sensitive to pH changes.

"PEG-HCCs have enormous capacity to convert superoxide to oxygen and the ability to quench reactive intermediates while not affecting nitric oxide molecules that are beneficial in normal amounts," Kent said. "So they hold a unique place in our potential armamentarium against a range of diseases that involve loss of oxygen and damaging levels of free radicals."

The study also determined PEG-HCCs remain stable, as batches up to 3 months old performed as good as new.

Explore further: Nanoparticles reboot blood flow in brain

More information: Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters, PNAS,

Related Stories

Nanoparticles reboot blood flow in brain

August 23, 2012

A nanoparticle developed at Rice University and tested in collaboration with Baylor College of Medicine (BCM) may bring great benefits to the emergency treatment of brain-injury victims, even those with mild injuries.

Stroke damage mechanism identified

November 27, 2014

Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims—and are now searching for drugs to block it.

A simple therapy for brain injury

June 27, 2008

Severe brain injury due to blunt force trauma could be reduced by application of a simple polymer, Polyethylene glycol or PEG, mixed in sterile water and injected into the blood stream – as reported in BioMed Central's ...

Recommended for you

Nano-decoy lures human influenza A virus to its doom

October 25, 2016

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic ...

New method increases energy density in lithium batteries

October 24, 2016

Yuan Yang, assistant professor of materials science and engineering at Columbia Engineering, has developed a new method to increase the energy density of lithium (Li-ion) batteries. He has built a trilayer structure that ...

Nanofiber coating prevents infections of prosthetic joints

October 24, 2016

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial ...


Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Feb 10, 2015
Another neat story that could really change the survival rate after a huge cut/bullet wound/ what ever.
Pretty cool stuff. It's amazing how seemingly simple future medicine is turning out to be. All we needed was the ability to create nano-particles in a controlled way. It really seems like future medicine should be much more complicated and hard to understand.
1 / 5 (1) Feb 10, 2015
Until approx 250 years ago when steel cooking vessels replaced copper, humans were ingesting up to 300 times our current intake of elemental & bound copper which is a very effective anti-oxidant and with its metabolisation by ferroxidase & store in cerruloplasmin is the only way humans can absorb iron effectively.

An example of a prehistoric man who would likely have died from infections due to his injuries had he lived during the last 250 years where copper was low eg from war wounds can be found here:-

All currently known pathogens causing disease & infection in mammals hate copper, they cannot survive long in those environments, many bacteria use iron as a catalyst for food production, so the double whammy of low ingested copper & inappropriate iron metabolisation in the last 250 or so years led to immense suffering from many opportunistic infections & compelled us to find effective antibiotics but, copper intake is still low...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.