A newly published perspective paper in Nature Nanotechnology describes an innovative nanoparticle-based approach designed to remove harmful proteins from the body. The advance could dramatically expand the ability to treat so-called “incurable” proteins and open up new possibilities for diseases such as dementia and brain cancer.
The work was led by Senior Professor of Nanomedicine Bingyang Shi at the University of Technology Sydney (UTS) in collaboration with Professor Kam Leong of Columbia University and Professor Meng Zheng of Henan University.
Why abnormal proteins cause disease
“Proteins are essential for almost every function in the body, but when they mutate, misfold, overproduce or accumulate in the wrong place, they can disrupt normal cellular processes and trigger disease,” Professor Shi said.
“Many conditions, including cancer, dementia and autoimmune disorders, are driven by abnormal proteins, and some have shapes or behaviors that make them particularly resistant to drug treatment.”
Introducing nanoparticle-mediated targeted chimeras
To address this challenge, the team created a new class of engineered nanoparticles called nanoparticle-mediated targeting chimeras (NPTACs). These microscopic particles can be tailored to bind to specific disease-related proteins and break them down.
The Nature Nanotechnology “Nanoparticle-Mediated Targeted Chimeras Transform Targeted Protein Degradation,” explores how the technology works and where it might be used. The original discovery behind the approach was first reported in Nature Nanotechnology in October 2024.
“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,” Professor Shi said.
Overcoming the limits of existing therapies
Targeted protein degradation is one of the fastest growing areas in biotechnology with great commercial interest. Companies like Arvinas have raised over $1 billion and secured major partnerships with Pfizer, Bayer and Roche.
Despite these dynamics, existing tools for protein degradation often struggle with limited access to tissues, unintended effects on healthy proteins, and complex manufacturing requirements. These problems have slowed progress in areas such as brain disorders and solid tumors.
“Our nanoparticle-based strategy overcomes these obstacles,” said Professor Shi.
Key benefits of the NPTAC platform
According to the researchers, the new technology offers several important advantages:
- It enables the degradation of intra- and extracellular proteins
- Tissue and disease targeting, including across the blood-brain barrier
- Plug-and-play modularity enabling rapid adaptation to different protein targets
- Scalable and clinically translatable; utilizing FDA-approved nanomaterials and industry-proven synthesis strategies
- Multifunctional integration, it can be combined with diagnostic or therapeutic capabilities
First results and future potential
Backed by multiple international patents, NPTACs have already produced encouraging preclinical results against major disease targets such as EGFR (a protein that often drives tumor growth) and PD-L1 (a protein that helps cancer cells evade the immune system).
“This advance paves the way for applications in oncology, neurology and immunology. It changes the way we think about nanoparticles – not only as delivery tools, but also as active therapeutic agents,” said Professor Shi.
“With the market for targeted protein degradation expected to exceed $10 billion by 2030, NPTACs provide a powerful platform for the next generation of smart and precision therapies.
“We are now seeking strategic industry partners to accelerate clinical development, license applications across therapeutics and prepare for regulatory approval,” he said.
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