Nav: Home

Nanoparticles: Acidic alert

April 17, 2020

Researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich have synthesized nanoparticles that can be induced by a change in pH to release a deadly dose of ionized iron within cells. This mechanism could potentially open up new approaches to the targeted elimination of malignant tumors.

Ions play crucial roles in all aspects of cell biology. They trigger signaling cascades, regulate enzyme activities and control the pH of the intra- and extracellular media. The concentrations of free ions are therefore tightly regulated, and sudden changes in their intracellular levels can induce programmed cell death. However, this very fact has made it difficult to elucidate the complex mechanisms that control ion concentrations in cells. Because cells act rapidly to block the import of excess ions, they effectively resist attempts to manipulate intracellular ion levels. A research team led by Hanna Engelke and Evelyn Ploetz (Faculty of Chemistry and Pharmacy, LMU) has now synthesized nanoparticles that make it possible - for the first time - to rapidly trigger the large-scale release of ionic iron within cells in a controlled manner. This in turn precipitates a form of inflammatory cell death known as pyroptosis, a type of reaction that is specific to cells of the innate immune system. According to the new study, which appears in the journal Advanced Materials, the ability to induce pyroptosis on demand could in principle be utilized to eliminate malignant cells, and to trigger an immune reaction that is specifically directed against cancers.

The rapid-release effect is a direct result of the structural properties of the nanoparticles, which belong to a class of substances known as metal-organic frameworks (MOFs). The interstices formed by these frameworks provide identical binding sites to which other substances - in this case, iron-oxygen complexes - can be specifically attached. "Structurally, these binding sites are tiny hexagons that are connected to each other by organic linker molecules," Ploetz explains. "MOFs can be thought of as scaffolds, and the pores within each nanoparticle are large enough to allow reaction partners to diffuse into them." In addition the nanoparticles are coated with lipids, which enables them to be taken up by cells.

Once inside the cell, the nanoparticles are transported into organelles called lysosomes, where they are degraded. "We were able to demonstrate that the rate of degradation depends on the pH of the extracellular medium. If the pH value is relatively low, as it is in an acidic milieu, degradation occurs rapidly, which results in a sudden and massive release of iron ions," Ploetz says. She and her colleagues suspect that this effect is attributable to the fact that, under mildly acidic conditions, the reduced form of the amino acid cysteine - which promotes the dissolution of the nanoparticles - is present in excess.

"We were particularly surprised to find that the release of iron from the nanoparticles did not induce ferroptosis, as one might expect in the presence of excess iron. Instead, they trigger a reaction known as pyroptosis," says Ploetz. Induction of pyroptosis in cells of the innate immune system results in a strong inflammatory reaction, which kills the cell concerned, but may serve as a signal that activates anti-tumor immunity.

The authors point out that these nanoparticles have great potential as therapeutic agents, particularly in the treatment of malignant tumors. "The extracellular medium within tumors is more acidic than that associated with normal cells. In principle, this pH difference could be exploited for the targeted release of the iron within the tumor environment. That would enable the nanoparticles to attack the primary tumor directly, while inducing pyroptosis to activate the immune system," says Ploetz. "But because their properties can be readily controlled by altering the pH, they are also ideally suited for application in other contexts."
-end-
Advanced Materials 2020

Ludwig-Maximilians-Universität München

Related Immune System Articles:

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.