Innovative gradient-free cancer traps: mechanically guided capture of metastatic cells for enhanced therapeutic efficacy

Current treatments for cancer, including chemotherapy, radiotherapy, and surgery, have demonstrated positive outcomes in general; however, their efficacy is hindered by limitations in addressing metastatic tumors originating from infiltrating cells that escape the primary treatment. This shortfall significantly contributes to the rising number of cancer-related deaths and emphasizes the need for innovative therapeutic strategies. Treatment effectiveness can be enhanced by employing bioengineered cancer traps—implantable devices designed to attract infiltrating cancer cells and prevent their uncontrolled spread in vivo, and potentially enable eradication. Traditional cancer traps typically rely on chemoattractant-loaded materials, where the generated gradients may evolve unpredictably triggering adverse effects on other cells, leading to unwanted responses.

In this study, we have engineered innovative gradient-free cancer traps featuring arrays of microstructured channels organized in an annular morphology. Each channel contains asymmetric and interconnected triangular features, with the pointed edge oriented towards the center of the trap. Fabricated through soft lithography using biocompatible materials, this trap design mechanically attracts metastatic cancer cells and guides their migration following a ratchet mechanism for their selective capture over extended periods, notably in the absence of chemoattractants.

In vitro assays demonstrated a significant trapping efficiency of the ratchet-like traps against highly disseminating MDA-MB-231 breast cancer cells. Leveraging their 3D-like architecture, the traps functioned as asymmetric potential wells, mechanically entrapping cells within short periods when uniformly deposited at their top (Figure 1). Once captured, the mechanical interaction between the cell nuclei and the topographical walls of the trap dictated the preferred direction of migration, mainly towards the pointed edge of the asymmetric triangles (60±5%), elucidating a clear bias and the operation mechanism of the ratchet traps. This process exploited by cells to transition across adjacent topographic features with a high persistence length and time. As a result of this cyclic process, cancer cells accumulated in the inner region of the trap, showing a >100% increase of captured cells compared to control –isotropic– conditions, showcasing the trap bias effect. Importantly, the traps exhibited reduced efficacy when targeting non-metastatic and non-tumorigenic cells, underscoring their suitability for specifically capturing highly invasive cancer cells. Finally, the traps demonstrated the capability to restrict the spread of cancer cells when infiltrating breast cancer micro-spheroids were seeded at their center. This was achieved by reversing the motion of cells, thereby mitigating their invasion.

Overall, this original approach holds promising implications for combating cancer and for being employed as a research tool for attracting, capturing, and eliminating disseminating cancer cells, thus potentially providing valuable insights into the biology and behavior of cancer cells. Furthermore, these traps hold the potential for isolating cancer cells for further in-depth analysis, which could enhance our understanding of cancer progression and metastasis.