Researchers have developed a new nanomaterial platform that combines nanozymes with antibody targeting to improve the precision and effectiveness of treatment in HER2-positive cancer models.
Their goal is to block transcriptional processes that support tumor growth and spread by disrupting gene expression pathways central to cancer progression.
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Background
HER2 (human epidermal growth factor receptor 2) is overexpressed in a subset of breast cancers and is associated with poor prognosis and aggressive tumor behavior. Existing therapies, including monoclonal antibodies like trastuzumab, have improved survival but remain limited by resistance, side effects such as cardiotoxicity, and incomplete tumor clearance. The complexity of HER2 signaling and the tumor microenvironment means that more adaptable and targeted strategies are needed.
Nanozymes—nanomaterials that mimic enzyme activity—offer advantages such as chemical stability, customizable properties, and multiple therapeutic functions. When linked with antibodies, they can be directed precisely to tumor cells, potentially increasing treatment accuracy and reducing side effects.
The Current Study
The researchers developed bimetallic nanozymes by combining two different metals in a nanostructured design optimized for catalytic function. These nanozymes were then linked to anti-HER2 monoclonal antibodies to allow specific targeting of HER2-positive tumors. The fabrication process was tightly controlled to produce uniform size, shape, and surface characteristics that support catalytic activity.
They used transmission electron microscopy (TEM), X-ray diffraction (XRD), and surface analysis techniques to thoroughly characterize the nanozymes. To evaluate targeting accuracy, the particles were labeled with fluorescent tags and tracked both in cell cultures and in live animal models using fluorescence imaging.
Safety and compatibility were assessed through hemolysis tests, blood toxicity evaluations, and tissue analysis after the nanozymes were injected into mice. The treatment's effectiveness was tested in HER2-positive tumor models, including breast cancer xenografts. Nanozymes were administered intravenously at defined doses and intervals.
Researchers monitored tumor response through imaging, tumor size measurement, and tissue examination, focusing on whether the treatment reduced metastasis and altered gene activity. They used molecular methods, such as Western blotting, to study protein levels related to HER2 signaling, cell death, and cell cycle regulation. Additional in vivo tests assessed toxicity, distribution throughout the body, and immune response to confirm targeted action and overall safety.
Results and Discussion
The bimetallic nanozymes showed strong catalytic activity and were able to disrupt signaling pathways in tumor cells. Targeted distribution studies confirmed that, when linked to HER2-specific antibodies, the nanozymes concentrated in HER2-positive tumors. Their accumulation increased over time following injection.
In cell-based experiments, the nanozymes significantly reduced the growth of HER2-positive cancer cells. This effect was mainly due to transcriptional interference that lowered the expression of genes involved in tumor growth and spread. Western blot analysis showed reduced levels of phosphorylated HER2 and downstream proteins such as AKT and ERK, key components of the HER2 signaling pathway. The nanozymes also triggered apoptosis and cell cycle arrest, further limiting tumor cell survival.
In live animal studies, the treatment was well-tolerated. The nanozymes caused minimal damage to red blood cells and showed no major toxicity in organs, as confirmed by tissue analysis and standard blood tests.
Mice treated with the nanozymes had slower tumor growth and fewer lung metastases compared to untreated controls. Imaging and tissue studies confirmed that the nanozymes reached the tumor site and remained there. Analysis of lung tissue also showed a clear reduction in metastatic nodules in treated animals.
These findings suggest that the antibody-linked catalytic nanozymes can effectively interfere with gene expression programs that support tumor growth and metastasis.
Conclusion
This study presents a new class of antibody-guided bimetallic nanozymes that can selectively target HER2-positive tumors and interfere with gene expression linked to cancer progression. The nanozymes are catalytically active, accumulate efficiently in tumors, and appear safe in vivo, offering a promising approach to control metastasis.
Integrating nanotechnology, enzymatic functions, and immune targeting, this platform may complement or enhance current therapies. Future research will focus on improving stability, expanding to other cancer targets, and assessing long-term outcomes in clinical models.
Journal Reference
Miao, H. et al. (2025). Antibody-Programmable Bimetallic Nanozymes for Transcriptional Blockade Therapy in HER2. Advanced Functional Materials, DOI:10.1002/adfm.202508310, https://advanced.onlinelibrary.wiley.com/doi/10.1002/adfm.202508310