Lab-engineered proteins: A promising treatment for liver disease
· Medical Xpressedited by Lisa Lock, reviewed by Robert Egan
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The research group led by CIC biomaGUNE's Ikerbasque Research Professor Aitziber L. Cortajarena has developed an innovative anti-fibrotic and anti-tumor treatment by binding a synthetic protein to gold nanoclusters (small aggregates of approximately 6 atoms of gold). Conducted in collaboration with the group led by Dr. Ana Beloqui at the Catholic University of Louvain (Belgium), the study, published in Bioactive Materials, has demonstrated that this hybrid formulation displays strong hepatic specificity and minimal side effects in mice.
Liver diseases can progress from reversible inflammation to chronic conditions, such as liver fibrosis and liver cancer. Fibrosis is characterized by the progressive buildup of scar tissue in the early stages, eventually leading to the development of tumors and liver failure in advanced stages. According to the WHO, 830,000 deaths due to hepatocellular carcinoma were recorded worldwide in 2020. Furthermore, it is estimated that around 3.3% of the global population suffers from advanced liver fibrosis.
In recent years, considerable effort has gone into developing therapeutic strategies aimed at blocking the function of the Hsp90 protein because of its central role in fibrosis and cancer progression. Synthetic protein molecules have emerged as an attractive alternative because they can be rationally engineered to recognize specific targets, and their therapeutic activity can be optimized.
In this respect, the hybrid material developed by CIC biomaGUNE's Biomolecular Nanotechnology group, in collaboration with the Advanced Drug Delivery and Biomaterials group at the Louvain Drug Research Institute, is engineered to bind to the Hsp90 protein, in much the same way as a key fits into a lock.
"That way, the processes that trigger the disease are blocked as excessive amounts of this protein are found in diseased livers," explained Dr. Cortajarena, scientific director of CIC biomaGUNE. "The results of the study show that the compound developed is a promising, state-of-the-art therapy that elicits a low immune response and offers high therapeutic potential."
In the case of liver fibrosis, the treatment developed reduces liver damage. The team was able to verify that there was a reduced presence of molecules that trigger the disease, as well as a reduction in the accumulated collagen fibers. In other words, it applies a brake to the mechanism that causes scarring while removing tissue that has already been damaged.
In the case of liver cancer, the results are equally promising: Blocking the Hsp90 protein leads to a reduction in the proteins that allow cancer cells to divide uncontrollably. Thanks to this biological "braking" mechanism, the research team managed to significantly reduce both the number and size of the tumors, a breakthrough it was able to confirm using various imaging and molecular analysis techniques.
For therapy, monitoring and diagnosis
Meanwhile, the presence of the gold nanocluster enabled "the distribution of the drug in the mouse to be detected, thus making it possible to investigate the organs in which it had built up; this is key information when it comes to understanding its behavior in the body and, therefore, to developing effective drugs," said Gabriela Guedes, one of the researchers participating in the study.
"It is important to highlight the fact that the versatility of these engineered proteins opens up the possibility of adapting the metal component to the desired imaging technique modality," said Cortajarena. The protein structure can be engineered so that, aside from gold, it can bind in a stable way to other metals, such as gadolinium or iron, which gives the therapeutic system the ability to be tracked using a range of imaging and diagnostic techniques.
For example, "the binding of iron-based nanostructures to the engineered protein would allow treatment to be monitored in real time using magnetic resonance imaging without the need to administer an additional contrast agent," added the Ikerbasque Research Professor.
The researchers concluded that this study provides evidence not only for the potential of the engineered protein as an antifibrotic and anti-tumor agent, but also for its versatility in developing it as a theranostic agent, in other words, one that fulfills both therapeutic and diagnostic functions. These results open up countless opportunities for improving patient treatment and outcomes: "Our findings offer new possibilities for developing therapies based on proteins of this type."
Publication details
Tanya Saxena et al, Engineered protein nanoclusters reduce liver fibrosis and hepatocellular carcinoma in mice models, Bioactive Materials (2026). DOI: 10.1016/j.bioactmat.2026.05.038
Journal information: Bioactive Materials
Key medical concepts
Liver FibrosisHSP90 Heat-Shock ProteinsCarcinoma, Hepatocellular
Clinical categories
GastroenterologyOncologyClinical pharmacology Provided by CIC biomaGUNE Who's behind this story?
Lisa Lock
BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →
Robert Egan
Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →
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