Researchers at the Hebrew University of Jerusalem have developed a new method to detect aggressive and metastatic cancer cells by how they physically interact with specially textured Meta surfaces patterned with tiny immobilized particles. The research, published in the journal Materials Today Bio, found that more aggressive cancer cells gripped the nanoparticle embedded on the surface more strongly, swallowed more particles and altered their shape in ways that were different from less aggressive cells. The breakthrough could significantly improve current cancer diagnostic methods that largely rely on genetic or protein markers for diagnosis.
The study was led by PhD student Chalom Zemmour in the lab of Ofra Benny, PhD, a professor and director of the Fraunhofer Project Center for Drug Discovery and Delivery at Hebrew University of Jerusalem. “Much of our effort is focused on understanding how cancer cells interact with nanomaterials and small dimensions of materials that are loaded with drugs,” Benny said, adding that this understanding is essential for both diagnostics and precision oncology. The work also showed the ability to differentiate between cancer cells at varying stages of metastasis as those cells lose their ability to adhere to the nanosurface. The team theorizes that this allows the cancer cells to move more easily through the body before resuming growth and strong adhesion at a new site.
“This tells us that that aggressiveness is not a fixed trait and we can have a sensitive technology to measure it,” Benny said. “It’s a functional state that can be revealed through physical behavior, not just molecular signatures.”
Current diagnostic methods such as genetic sequencing and molecular biomarker analysis have significantly impacted the delivery of precision cancer care but do have limitations, such as high cost, long turnaround times, and often the inability to discern the functional behaviors that make some tumors more aggressive. Benny noted that understanding the physical properties of cancer cells can aid in therapy selection. “In many cases, cancer therapies and existing drugs are still quite vicious and not selective, harming healthy cells as well as tumor cells,” Benny said, which shows there is a need for better understanding of cancer cell function.
The lab’s development of what is being called mechanophenotyping represents a shift toward functional, phenotype-based cancer diagnostics able to the identify physical characteristics of cancer cells molecular profiling can’t.
The new technology comprises non-close-packed polystyrene bead arrays that are deposited on cell culture plates and stabilized with a thin silicon oxide coating to create controlled micro- and nano-topographies. These patterned surfaces resemble a landscape of isolated features many thousands of times smaller than a grain of sand. When cancer cells are placed on them, their interactions with the surface—such as how they adhere, spread, deform, and internalize particles, reveal the distinct mechanophenotypes that identify malignant cell forms and behaviors.
“Particle uptake differences were most pronounced for particle diameters above 0.5 μm, whereas adhesion differences emerged predominantly on particles ≥0.7 μm and increased progressively with larger particle sizes,” the researchers noted. More aggressive cancer cells showed stronger adhesion, more extensive actin-rich protrusions, and greater particle uptake than less aggressive cells. The teams then used these measurable traits to classify different levels of malignancy. According to Benny, these physical traits can ultimately guide how nanoparticles are engineered for optimal drug delivery.
The creation of a landscape, as opposed to a flat surface is the key to the performance of the new technology. By creating micro- and nano-features across a range of sizes and densities, the platform activates biomechanical responses in the cells that would not be detectable on flat or conventional surfaces.
This research builds on a broad foundation of work in Benny’s laboratory which has multiple areas of research on the interface between nanotechnology, bioengineering, and cancer biology. In addition to nanoengineering, the lab is developing advanced drug delivery systems based on nanomedicine and smart materials, including tumor-on-a-chip technologies to inform precision oncology via personalized therapy testing. At its heart, the Benny lab is looking to leverage a better understanding of the cell-material interactions that can be exploited to develop both personalized therapies and diagnostics.
Understanding the physical properties of cancer cells can be just as important as knowing their molecular makeup, Benny noted. “We found that the physical parameters of cancer cells have a major effect on how they absorb drugs or nanoparticle-based drugs.”
An important feature of the new platform is that it could easily be incorporated into existing imaging and molecular workflows, making it adaptable for high-throughput research or clinical use. For example, it could serve as a rapid screening tool for cancer cell aggressiveness, a way to study tumor progression and metastasis, as well as a method to evaluating drug responses without the need for fluorescent labels or molecular assays.
The team noted that by directly probing cell mechanophenotype such as adhesion and deformability, the new platform not only offers a potentially new diagnostic method but also provides a method for better understanding of how biomechanical traits evolve during cancer progression.
The researchers will now seek to study a broader range of cancer types, primary tumor-derived cells, and patient-derived samples and continuing exploring how adhesion modulation and particle uptake relate to gene expression and metastatic behavior. The intent is to translate the platform into clinical tools that could aid in identifying aggressive cell populations within tumor masses and potentially guide personalized treatment decisions. “Our goal is to tailor the right therapy so patients can live longer and have a better quality of life,” Benny said.
