Scientists have developed a new nanoparticle-based strategy that could dramatically expand the range of disease-causing proteins that can be targeted by modern medicine.
A newly released perspective in Nature Nanotechnology describes an emerging nanoparticle-based approach designed to remove harmful proteins that drive disease. By expanding the range of proteins that can be therapeutically targeted, the technology offers a new pathway for addressing conditions such as dementia and brain cancer that have remained difficult to treat.
The work was led by Chair Professor in 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.
“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,” said Professor Shi.
“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 treatments.”
Engineering Nanoparticles to Target Proteins
To tackle these challenges, the researchers created a new type of engineered nanoparticle called nanoparticle-mediated targeting chimeras (NPTACs). The particles are designed to recognize specific disease-associated proteins and promote their breakdown within the body.
The Nature Nanotechnology perspective explores how this technology works and outlines its possible medical uses. The team’s original experimental findings were also 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,” said Professor Shi.
Interest in targeted protein degradation has surged in recent years, making it one of the fastest-growing sectors in biotechnology. Companies such as Arvinas have attracted more than $1 billion USD in investment and formed major partnerships with pharmaceutical firms including Pfizer, Bayer, and Roche.
Despite this progress, existing protein degradation technologies face important limitations. Challenges such as limited tissue penetration, unintended interactions with other proteins, and complex chemical design have slowed their use, particularly for brain disorders and solid tumors.
“Our nanoparticle-based strategy overcomes these bottlenecks,” said Professor Shi.
Key Advantages and Early Results
The researchers highlight several key advantages of the NPTAC platform:
- Enabling degradation of both intra- and extracellular proteins
- Tissue- and disease-specific targeting, including across the blood–brain barrier
- Plug-and-play modularity, enabling rapid adaptation to diverse protein targets
- Scalable and clinically translatable; leveraging FDA-approved nanomaterials and industry-proven synthesis strategies
- Multifunctional integration, can combine with diagnostic or therapeutic capabilities.
Protected by multiple international patents, NPTACs have already shown strong preclinical results against key disease targets such as EGFR (a protein often driving tumor growth) and PD-L1 (a protein that helps cancer cells evade the immune system).
“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,” said Professor Shi.
“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, license applications across therapeutic fields, and prepare for regulatory approval,” he said.
Reference: “Nanoparticle-mediated targeting chimeras transform targeted protein degradation” by Yang Liu, Xue Xia, Yunjiao Zhang, Meng Zheng, Kam W. Leong and Bingyang Shi, 20 January 2026, Nature Nanotechnology.
DOI: 10.1038/s41565-025-02081-1
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