Magnetic nanoparticles targeting Alzheimer’s disease

AIBN researchers have designed multifunctional magnetic nanoparticles that could offer a new way to detect and treat Alzheimer’s disease.

The nanoparticles recognise amyloid-beta (amyloid-β), a small protein fragment associated with Alzheimer’s disease, and prevent it from joining together to form long, toxic fibres.

The nanoparticles also contain a magnetic core that can be seen using magnetic resonance imaging (MRI), potentially allowing researchers to locate and monitor amyloid-β in the brain.

Associate Professor Ruirui Qiao and Dr Ao Shen used polymer engineering to give the nanoparticles several complementary functions.

“The ‘plug and play’ modular design of the polymers allows us to combine several properties at once – for targeting, therapy and imaging,” Dr Qiao said.

Interrupting amyloid-β assembly

Alzheimer’s disease involves many complex biological processes, but the researchers focused on amyloid-β because it remains one of the disease’s most widely studied biomarkers and drug targets.

One of the features of Alzheimer’s disease is the accumulation of amyloid-β plaques, formed through the aggregation of amyloid-β into fibres, which are associated with cognitive decline and memory loss.

These new magnetic nanoparticles interact with the early amyloid-β species and inhibit their assembly into mature fibres.

A magnetic core with an adaptable shell

Each nanoparticle has an iron oxide core surrounded by an engineered polymer shell.

The iron oxide core acts as a contrast agent for MRI, while the chemistry of the polymer shell controls how the nanoparticle behaves in a biological environment.

“The magnetic nanoparticles are a wonderful tool for serving as a contrast enhancement in MRI – to enhance the contrast between the diseased tissue and the healthy tissue,” Dr Qiao said.

Iron oxide is an alternative to gadolinium-based MRI contrast agents, which not all patients can tolerate.

Current approaches for diagnosing Alzheimer’s disease include positron emission tomography (PET), analysing cerebrospinal fluid and MRI – all methods have their limitations.

MRI offers detailed images of the brain but has limited ability to identify specific molecules.

A contrast agent that directly targets amyloid-β could help address this shortcoming.

Dr Qiao’s specialty is engineering the surface of the polymers for different purposes, which provides considerable versatility, for example attaching a drug or pursuing a disease target.

Crossing the blood brain barrier

One of the greatest challenges in developing treatments for brain diseases is the blood-brain barrier.

The barrier protects the brain from potentially harmful substances in the bloodstream, but it can also prevent promising treatments from reaching their intended target.

The researchers tested the nanoparticles using an in vitro cellular model designed to resemble this barrier.

Dr Qiao cautioned that no in vitro model can perfectly reproduce the complexity of the actual blood-brain barrier nor guarantee behaviour in the human brain.

Further research will be needed to determine how the nanoparticles behave in living systems.

“We are now exploring whether intranasal delivery could offer a non-invasive way to transport nanoparticles from the nose to the brain, bypassing the blood-brain barrier completely,” said Dr Qiao.

Using the magnets to guide future treatments

In the longer term, the magnetic properties of the nanoparticles could offer another level of control.

Many treatments for neurological diseases cannot precisely target the areas of the brain.

This can make treatments less effective and increase the risk of unwanted side effects on healthy tissue.

In the future, external magnetic fields could help guide nanoparticles to specific regions of the brain, enabling more precise delivery of drugs to where they are needed.

This could potentially help concentrate imaging agents or treatments at their intended target while reducing their effect on healthy tissue.

“One of the most promising aspects of this technology is the possibility of using a magnetic field to guide nanoparticles to a targeted area,” said Dr Qiao.

“I’m very excited about the potential opportunities for diagnostics, targeted drug delivery and personalised medicine.”

This research is published in Advanced NanoBiomed Research.

The study was led by Ao Shen and included Professor Ruirui Qiao, Professor Thomas Davis, Dr Liwen Zhang, Dr Helen Forgham, Jiayuan Zhu, Dr Xumin Huang, Dr Changkui Fu and Dr Ibrahim Javid.

The researchers used AIBN’s Centre for Advanced Imaging, Australian National Fabrication Facility (ANFF) and Centre for Microscopy and Microanalysis (CMM) – NCRIS-enabled and housed at AIBN.