Rational Design of Drug Delivery Systems for Selective Cancer Therapy

Understanding the complexity of tumor biology and the underlining cellular processes involved in disease progression, emphasizes the need to identify varying cell behaviors that can be integrated to reveal clinical relevant information. The effort to detect molecular biomarkers for targeted therapy are limited by the dynamic nature of cellular molecular pattern and their heterogeneity. Measuring mechanical properties of cancer cells was suggested as a complimentary approach that can detect malignant features of cancer cells. Here we provide a comprehensive study that provide a trio correlation between cell mechanics, their tendency to interact with particles in a phagocytic-like manner, and their aggressiveness. By bi-directional study we found that the capacity for particle uptake is an imprinted cell behavior and “phagocytic” cancer cell population can be enriched over time, and correlate with higher malignancy and greater deformability and adhesion as demonstrated in vitro and in vivo. In agreement, greater malignancy was correlated with higher particle uptake and less rigid phenotype. Our study provides new mechanistic insights related to the role of mechanical tuning during cancer progression, and, importantly to suggest a future direction of using particle uptake as diagnostic tool for precision medicine.