A nanoparticle based biosensor to prevent deadly diseases contracted on medical equipment?

via Monash University

Monash University researchers have gained insights into how nanoparticles could develop a biosensor to prevent deadly diseases contracted on medical equipment, such as catheters.
  • Monash University researchers have gained insights into how nanoparticles could develop a biosensor to prevent deadly diseases contracted on medical equipment, such as catheters.
  • Candida albicans can become a serious problem for people who are seriously ill or immune-suppressed.

Researchers at Monash University have gained insights into how nanoparticles could be used to identify the presence of invasive and sometimes deadly microbes, and deliver targeted treatments more effectively.

This study was conducted as an interdisciplinary collaboration between microbiologists, immunologists and engineers led by Dr Simon Corrie from Monash University’s Department of Chemical Engineering and Professor Ana Traven from the Monash Biomedicine Discovery Institute (BDI). It was recently published in the American Chemical Society journal ACS Applied Interfaces and Material.

Candida albicans, a commonly found microbe, can turn deadly when it colonises on devices such as catheters implanted in the human body. While commonly found in healthy people, this microbe can become a serious problem for those who are seriously ill or immune-suppressed.

The microbeforms a biofilm when it colonises using, for example, a catheter as a source of infection. It then spreads into the bloodstream to infect internal organs.

“The mortality rate in some patient populations can be as high as 30 to 40 per cent even if you treat people. When it colonises, it’s highly resistant to anti-fungal treatments,” Professor Traven said.

“The idea is that if you can diagnose this infection early, then you can have a much bigger chance of treating it successfully with current anti-fungal drugs and stopping a full-blown systemic infection, but our current diagnostic methods are lacking. A biosensor to detect early stages of colonisation would be highly beneficial.”

The researchers investigated the effects of organosilica nanoparticles of different sizes, concentrations and surface coatings to see whether and how they interacted with both C. albicans and with immune cells in the blood.

They found that the nanoparticles bound to fungal cells, but were non-toxic to them.

“They don’t kill the microbe, but we can make an anti-fungal particle by binding them to a known anti-fungal drug,” Professor Traven said.

The researchers also demonstrated that the particles associate with neutrophils – human white blood cells – in a similar way as they did with C. albicans, remaining noncytotoxic towards them.

“We’ve identified that these nanoparticles, and by inference a number of different types of nanoparticles, can be made to be interactive with cells of interest,” Dr Corrie said.

“We can actually change the surface properties by attaching different things; thereby we can really change the interactions they have with these cells – that’s quite significant.”

Dr Corrie said while nanoparticles were being investigated in the treatment of cancer, the use of nanoparticle-based technologies in infectious diseases lags behind the cancer nanomedicine field, despite the great potential for new treatments and diagnostics.

“The other unique thing in this study is that rather than using cells grown in culture, we’re also looking at how particles act in whole human blood and with neutrophils extracted from fresh human blood,” he said.

Professor Traven said the study had benefited greatly from interdisciplinary collaboration.

“We’ve brought together labs with expertise in infection, microbiology and immunology with a lab that has expertise in engineering, to do state-of-the-art experiments,” she said.

Learn more: Study points to new weapon in fight against lethal fungi

 

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Could nanoparticles eventually give built-in night vision to humans?

ORGANIC NANOPARTICLES IN A VIAL CONVERT INVISIBLE NEAR-INFRARED LIGHT TO INTENSE BLUE LIGHT, WHICH CAN EASILY BE SEEN BY HUMAN EYES

Movies featuring heroes with superpowers, such as flight, X-ray vision or extraordinary strength, are all the rage. But while these popular characters are mere flights of fancy, scientists have used nanoparticles to confer a real superpower on ordinary mice: the ability to see near-infrared light. Today, scientists report progress in making versions of these nanoparticles that could someday give built-in night vision to humans.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

“When we look at the universe, we see only visible light,” says Gang Han, Ph.D., the project’s principal investigator, who is presenting the work at the meeting. “But if we had near-infrared vision, we could see the universe in a whole new way. We might be able to do infrared astronomy with the naked eye, or have night vision without bulky equipment.”

The eyes of humans and other mammals can detect light between the wavelengths of 400 and 700 nanometers (nm). Near-infrared (NIR) light, on the other hand, has longer wavelengths — 750 nm to 1.4 micrometers. Thermal imaging cameras can help people see in the dark by detecting NIR radiation given off by organisms or objects, but these devices are typically bulky and inconvenient. Han and his colleagues wondered whether they could give mice NIR vision by injecting a special type of nanomaterial, called upconversion nanoparticles (UCNPs), into their eyes. These nanoparticles, which contain the rare-earth elements erbium and ytterbium, can convert low-energy photons from NIR light into higher-energy green light that mammalian eyes can see.

In work published earlier this year, the researchers, who are at the University of Massachusetts Medical School, targeted UCNPs to photoreceptors in mouse eyes by attaching a protein that binds to a sugar molecule on the photoreceptor surface. Then, they injected the photoreceptor-binding UCNPs behind the retinas of the mice. To determine whether the injected mice could see and mentally process NIR light, the team conducted several physiological and behavioral tests. For example, in one test, the researchers placed the mice into a Y-shaped tank of water. One branch of the tank had a platform that the mice could climb on to escape the water. The researchers trained the mice to swim toward visible light in the shape of a triangle, which marked the escape route. A similarly lit circle marked the branch without a platform. Then, the researchers replaced the visible light with NIR light. “The mice with the particle injection could see the triangle clearly and swim to it each time, but the mice without the injection could not see or tell the difference between the two shapes,” says Han.

Although the UCNPs persisted in the mice’s eyes for at least 10 weeks and did not cause any noticeable side effects, Han wants to improve the safety and sensitivity of the nanomaterials before he contemplates trying them out in humans. “The UCNPs in our published paper are inorganic, and there are some drawbacks there,” Han says. “The biocompatibility is not completely clear, and we need to improve the brightness of the nanoparticles for human use.” Now, the team is experimenting with UCNPs made up of two organic dyes, instead of rare-earth elements. “We’ve shown that we can make organic UCNPs with much improved brightness compared with the inorganic ones,” he says. These organic nanoparticles can emit either green or blue light. In addition to having improved properties, the organic dyes could also have fewer regulatory hurdles.

One of the next steps for the project might be translating the technology to man’s best friend. “If we had a super dog that could see NIR light, we could project a pattern onto a lawbreaker’s’ body from a distance, and the dog could catch them without disturbing other people,” Han says. Superhero powers aside, the technology could also have important medical applications, such as treating diseases of the eye. “We’re actually looking at how to use NIR light to release a drug from the UNCPs specifically at the photoreceptors,” Han says.

Learn more: Nanoparticles could someday give humans built-in night vision

 

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A promising therapeutic approach to halt and potentially reverse plaque buildup in arteries

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In a new Yale-led study, investigators have revealed previously unknown factors that contribute to the hardening of arteries and plaque growth, which cause heart disease. Their insight is the basis for a promising therapeutic approach to halt and potentially reverse plaque buildup and the progression of disease, the researchers said.

The study was published online by Nature Metabolism.

Current treatments for plaque and hardened arteries, a condition known as atherosclerosis, can slow but not improve the disease. Experts believe that may be due to ongoing inflammation in blood vessels. To understand the factors contributing to this inflammation, the research team focused on a group of proteins, called transforming growth factor beta (TGFß), that regulates a wide range of cells and tissues throughout the body.

Using cultured human cells, the researchers discovered that TGF? proteins trigger inflammation in endothelial cells — the cells that form the inner lining of artery walls — but not in other cell types. With a technique called single cell RNA-seq analysis, which measures the expression of every gene in single cells, they then showed that TGF? induced inflammation in these cells in mouse models. This finding was notable, said the researchers, because TGF? proteins are known to decrease inflammation in other cells in the body.

The researchers also showed that when the TGF? receptor gene is deleted in endothelial cells, both the inflammation and plaque in blood vessels are significantly reduced.

To test this approach as a potential therapy, the team, led by professor of medicine Michael Simons, M.D., used an “interfering” RNA, or RNAi, drug developed at Yale, to disrupt TGFß receptors. Interfering RNA use a gene’s own DNA sequence to turn off or silence the gene. To deliver the drug only to endothelial cells in the blood vessel walls of mice, they employed microscopic particles, or nanoparticles, created by their co-authors at MIT. This strategy reduced inflammation and plaque as effectively as the genetic technique.

The findings identify TGFß signaling as a major cause of chronic vessel wall inflammation, and demonstrate that disruption of this pathway leads to cessation of inflammation and substantial regression of existing plaque, said the scientists.

Based on this discovery, investigators at Yale and MIT have launched a biotech company, VasoRX, Inc., to develop this targeted approach, using the RNAi drug delivered by nanoparticles as a potential therapy for atherosclerosis in people.

Learn more: Yale-led study offers promising approach to reducing plaque in arteries

 

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A new way to determine whether or not single drug-delivery nanoparticles will successfully hit their intended targets

Gold nanostars have emerged as promising drug-delivery agents that can be designed to target cancer cells

Targeting nanoparticles rotate faster and move across larger areas

Targeted drug-delivery systems hold significant promise for treating cancer effectively by sparing healthy surrounding tissues. But the promising approach can only work if the drug hits its target.

A Northwestern University research team has developed a new way to determine whether or not single drug-delivery nanoparticles will successfully hit their intended targets — by simply analyzing each nanoparticle’s distinct movements in real time.

By studying drug-loaded gold nanostars on cancer cell membranes, the researchers found that nanostars designed to target cancer biomarkers transited over larger areas and rotated much faster than their non-targeting counterparts. Even when surrounded by non-specifically adhered proteins, the targeting nanostars maintained their distinct, signature movements, suggesting that their targeting ability remains uninhibited.

“Moving forward, this information can be used to compare how different nanoparticle characteristics — such as particle size, shape and surface chemistry — can improve the design of nanoparticles as targeting, drug-delivery agents,” said Northwestern’s Teri Odom, who led the study.

The study published today (Aug. 9) in the journal ACS Nano. Odom is the Charles E. and Emma H. Morrison Professor of Chemistry in Northwestern’s Weinberg College of Arts and Sciences.

The medical field has long been searching for alternatives to current cancer treatments, such as chemotherapy and radiation, which harm healthy tissues in addition to diseased cells. Although these are effective ways to treat cancer, they carry risks of painful or even dangerous side effects. By delivering drugs directly into the diseased area — instead of blasting the whole body with treatment — targeted delivery systems result in fewer side effects than current treatment methods.

“The selective delivery of therapeutic agents to cancer tumors is a major goal in medicine to avoid side effects,” Odom said. “Gold nanoparticles have emerged as promising drug-delivery vehicles that can be synthesized with designer characteristics for targeting cancer cells.”

Various proteins, however, tend to bind to nanoparticles when they enter the body. Researchers have worried that these proteins might impede the particles’ targeting abilities. Odom and her team’s new imaging platform can now screen engineered nanoparticles to determine if their targeting function is retained in the presence of the adhered proteins.

Learn more: Nanoparticles’ movement reveals whether they can successfully target cancer

 

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The potential to prevent some spinal cord injuries from resulting in paralysis

Illustration of the human body showing the skeletal system, with the lower spine highlighted in red to indicate pain spots. Image courtesy: Michigan Engineering

An injection of nanoparticles can prevent the body’s immune system from overreacting to trauma, potentially preventing some spinal cord injuries from resulting in paralysis.

The approach was demonstrated in mice at the University of Michigan, with the nanoparticles enhancing healing by reprogramming the aggressive immune cells—call it an “EpiPen” for trauma to the central nervous system, which includes the brain and spinal cord.

“In this work, we demonstrate that instead of overcoming an immune response, we can co-opt the immune response to work for us to promote the therapeutic response,” said Lonnie Shea, the Steven A. Goldstein Collegiate Professor of Biomedical Engineering.

Trauma of any kind kicks the body’s immune response into gear. In a normal injury, immune cells infiltrate the damaged area and clear debris to initiate the regenerative process.

The central nervous system, however, is usually walled off from the rough-and-tumble of immune activity by the blood-brain barrier. A spinal cord injury breaks that barrier, letting in overzealous immune cells that create too much inflammation for the delicate neural tissues. That leads to the rapid death of neurons, damage to the insulating sheaths around nerve fibers that allow them to send signals, and the formation of a scar that blocks the regeneration of the spinal cord’s nerve cells.

All of this contributes to the loss of function below the level of the injury. That spectrum includes everything from paralysis to a loss of sensation for many of the 12,000 new spinal injury patients each year in the United States.

Previous attempts to offset complications from this immune response included injecting steroids like methylprednisolone. That practice has largely been discarded since it comes with side effects that include sepsis, gastrointestinal bleeding and blood clots. The risks outweigh the benefits.

But now, U-M researchers have designed nanoparticles that intercept immune cells on their way to the spinal cord, redirecting them away from the injury. Those that reach the spinal cord have been altered to be more pro-regenerative.

Hopefully, this technology could lead to new therapeutic strategies not only for patients with spinal cord injury but for those with various inflammatory diseases.
Jonghyuck Park

With no drugs attached, the nanoparticles reprogram the immune cells with their physical characteristics: a size similar to cell debris and a negative charge that facilitates binding to immune cells. In theory, their nonpharmaceutical nature avoids unwanted side effects.

With fewer immune cells at the trauma location, there is less inflammation and tissue deterioration. Second, immune cells that do make it to the injury are less inflammatory and more suited to supporting tissues that are trying to grow back together.

“Hopefully, this technology could lead to new therapeutic strategies not only for patients with spinal cord injury but for those with various inflammatory diseases,” said Jonghyuck Park, a U-M research fellow working with Shea.

Previous research has shown success for nanoparticles mitigating trauma caused by the West Nile virus and multiple sclerosis, for example.

“The immune system underlies autoimmune disease, cancer, trauma, regeneration—nearly every major disease,” Shea said. “Tools that can target immune cells and reprogram them to a desired response have numerous opportunities for treating or managing disease.”

Learn more: An ‘EpiPen’ for spinal cord injuries

 

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