Henan University

Researchers have developed smart nanoparticles that can seek out and destroy disease-causing proteins the body can’t normally eliminate. Unlike traditional drugs, these particles can reach hard-to-access tissues, including the brain, and precisely target problem proteins without widespread side effects. Early results show promise against major cancer drivers, and the platform is designed to be easily adapted to many diseases. The work could reshape the future of precision medicine.A newly released perspective article in Nature Nanotechnology describes an innovative nanoparticle-based approach designed to remove harmful proteins from the body. This advance could dramatically expand the ability to treat so-called "undruggable" proteins, opening new possibilities for diseases such as dementia and brain cancer. 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. Why Abnormal Proteins Cause Disease "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." Introducing Nanoparticle-Mediated Targeting 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 attach to specific disease-related proteins and break them down. The Nature Nanotechnology perspective, "Nanoparticle-mediated targeting chimeras transform targeted protein degradation," explores how this technology works and where it could be applied. 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," said Professor Shi. Overcoming Limits of Existing Therapies Targeted protein degradation is one of the fastest-expanding areas in biotechnology, with major commercial interest. Companies such as Arvinas have raised more than $1 billion USD and secured large partnerships with Pfizer, Bayer, and Roche. Despite this momentum, existing protein degradation tools often struggle with limited tissue access, unintended effects on healthy proteins, and complex manufacturing requirements. These issues have slowed progress in areas like brain disorders and solid tumors. "Our nanoparticle-based strategy overcomes these bottlenecks," said Professor Shi. Key Advantages of the NPTAC Platform According to the researchers, the new technology offers several important benefits: Early Results and Future Potential Backed by multiple international patents, NPTACs have already delivered encouraging preclinical results against major 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.