Nanoparticles target disease proteins in dementia

Scientists have developed a nanoparticle strategy to broaden which disease-causing proteins medicines can target, giving options for dementia and brain cancer.

A perspective outlines an approach designed to remove harmful proteins that drive disease. By broadening the proteins that can be treated, the technology could help tackle conditions such as dementia and brain cancer.

The work was led by chair professor in nanomedicine Bingyang Shi at the University of Technology Sydney, in collaboration with professor Kam Leong of Columbia University and professor Meng Zheng of Henan University.

Professor Shi said: “Proteins are essential for nearly every function in the body, but when they become mutated, misfolded, overproduced or build up in the wrong place, they can disrupt normal cell processes and trigger disease.

He added: “Many conditions, including cancer, dementia, and autoimmune disorders, are driven by abnormal proteins, and some have shapes or behaviours that make them particularly resistant to drug treatments.”

To tackle these challenges, the researchers created a type of engineered nanoparticle called nanoparticle-mediated targeting chimeras (NPTACs).

The particles are designed to recognise specific disease-associated proteins and promote their breakdown in the body.

Professor Shi said: “We have developed an efficient and flexible method to guide disease-causing proteins, whether inside or outside the cell, into the body’s natural recycling system, where they can be broken down and removed.”

Interest in targeted protein degradation has surged in recent years.

Companies such as Arvinas have attracted more than US$1bn in investment and formed partnerships with pharmaceutical firms including Pfizer, Bayer and Roche.

However, existing protein degradation technologies face limitations.

Challenges such as poor tissue penetration, unintended interactions with other proteins and complex chemical design have slowed their use, particularly for brain disorders and solid tumours.

Professor Shi said: “Our nanoparticle-based strategy overcomes these bottlenecks.”

The researchers say the NPTAC platform can enable degradation of both proteins inside and outside cells, offers tissue and disease-specific targeting including across the blood-brain barrier (the protective barrier around the brain), and has plug-and-play modularity to adapt to diverse protein targets.

They say it is scalable and clinically translatable, leveraging FDA-approved nanomaterials and industry-proven synthesis strategies, and can combine with diagnostic or therapeutic capabilities.

Protected by multiple international patents, NPTACs have shown preclinical results against targets such as EGFR (a protein often driving tumour growth) and PD-L1 (a protein that helps cancer cells evade the immune system).

Professor Shi said: “This progress paves the way for applications in oncology, neurology, and immunology. It changes how we think about nanoparticles, not only as delivery tools but also as active therapeutic agents.

He added: “With the targeted protein degradation market expected to surpass $10 billion USD by 2030, NPTACs provide a powerful platform for the next generation of smart, precision therapies.

“We are now seeking strategic industry partners to accelerate clinical development, licence applications across therapeutic fields, and prepare for regulatory approval.”