Harnessing nanotechnology to deliver Selenium for stroke treatment

Stroke affects around 100,000 people in the UK every year and is a leading cause of death and disability. The most common type of stroke is an ischemic stroke, which occurs when blood flow to the brain is blocked, depriving brain cells of oxygen and nutrients. When blood flow is restored, even more damage is caused by oxygen returning to already damaged tissue and drives the production of harmful molecules known as reactive oxygen species (ROS) in large amounts. These molecules damage brain cells and trigger inflammation, leading to further cell death. This process is called ischemia-reperfusion injury.

One important type of cell death involved in stroke is pryoptosis, a highly inflammatory process that worsens brain injury. Although the body has a natural defence system to reduce this damage, it often becomes overwhelmed during a stroke. A major challenge in treating brain conditions like stroke is the blood-brain barrier preventing medicines from accessing the brain. This is a protective layer of tightly packed cells that line the blood vessels in the brain and act like a filter, preventing harmful substances in the blood from entering brain tissue. However, the barrier also makes it very difficult for many treatments to reach the brain, limiting how effective they can be.

Recent research has explored the use of antioxidant nanozymes. These are tiny, engineered particles that act similarly to enzymes to speed up biological reactions to reduce oxidative stress. Selenium is an essential mineral obtained through the diet that acts as an antioxidant to clear ROS (reactive oxygen species), form cellular antioxidant enzymes and plays a key role in protecting cells from damage. Selenium becomes depleted following stroke. Scientists have developed a selenium-based nanozyme that may help to reduce brain injury, but delivering these treatments to the brain remains a challenge. This study used tiny droplets of fat called liposomes to contain the selenium nanozymes and carry them across the blood brain barrier in a mouse model of stroke.

Why is the study important?

Current treatments for stroke mainly focus on restoring blood flow as quickly as possible. However, these treatments are often only effective within a short time window and are not suitable for many patients who aren’t seen within this window. Even when blood flow is restored, further damage can still occur due to inflammation and oxidative stress caused by ischemia-reperfusion injury. This study aimed to develop a new treatment that could reach the brain effectively and protect brain cells from damage after a stroke. If successful, this approach could improve recovery and reduce long-term disability in stroke patients.

What did the authors do and how did they do it?

The researchers developed a new treatment made up of selenium-doped carbon dots (tiny nanozyme particles with antioxidant properties) packaged inside small fat-based carriers called liposomes. These liposomes were modified with a substance called glutathione to help them cross the blood-brain barrier and target damaged brain tissue.

The treatment was tested in both lab grown cell models and in mice that had been given a stroke. In the mouse model, a temporary blockage was created in a brain artery using a clamp to mimic a human stroke, followed by restoration of blood flow. Researchers then assessed:

• Whether the treatment could cross the blood brain barrier to reach the brain
• Effect on levels of harmful molecules (ROS)
• The extent of brain cell death
• Brain damage size
• Survival and functional recovery of movement and learning abilities up to a month following treatment

They also examined the biological pathways to understand how the treatment worked at a molecular level

The study found that the selenium nanozyme had strong ROS scavenging abilities, was readily taken up by cellular neuronal models and protected them from oxidative damage. In mice, the treatment was safe, successfully reached the brain, reduced damage and improved outcomes after stroke. Survival at the 28 day mark was improved from 0% in the untreated mouse models to 70% in the highest dose treatment group. Specifically:

1. Levels of harmful ROS were significantly reduced
2. Brain cell death was decreased
3. The area of brain damage (infarct size) was smaller
4. Survival rates improved in a dose dependent manner
5. Mice showed improvements in movement and learning ability

At a biological level, the treatment increased levels of GPx4, a protective protein that helps control oxidative stress. This helped to maintain normal cell function and reduce the activation of inflammatory pathways that lead to pryoptosis. As a result, the treatment blocked a key chain of events that normally lead to inflammatory brain cell death after stroke.

What do the findings mean going forward for people with the disease?

These findings suggest that this nanozyme-based treatment could offer a new way to protect the brain after a stroke by reducing inflammation and preventing cell death. By targeting reperfusion injury rather than just restoring blood flow, this approach could potentially improve recovery and reduce long-term disability. It is important to note that the use of glutathione treated liposomes allowed for the nanozyme treatment to successfully target the brain following intravenous injection, overcoming one of the biggest challenges in stroke therapy. However, this research was only conducted in animals meaning that further studies in humans are needed to confirm if this treatment is a safe and effective option for patients. If successful, it could represent a promising new direction for stroke treatment.

This study can be found at
https://doi.org/10.1186/s12951-026-04107-9

Paper title
Selenium-doped carbon dots nanozymes hitchhiking tailored liposomes block neuronal pyroptosis through GPX4/ROS/NLRP3/GSDMD axis to attenuate ischemic stroke

Lead authors
Jiaxuan Hou, Hui Cai

Publication details including date of publication
Journal of Nanobiotechnology 24, 226 (2026).