Study of the interaction between nanoparticles and cancer cells in unicellular 3D models

Cancer is the second leading cause of death in industrialized countries. Tumors affect different organs and tissues; they are characterized by uncontrolled cells proliferation which impair function and structure of involved body area. The high mortality rate of cancer is due to generation of metastases, which seems to take place only in specific organs, mainly the liver. Mechanical properties of extracellular matrix are known to support cell survival and spreading and might therefore play a role in the metastatic spreading of cancer. Here, we aim to prepare different substrates of similar fibrous morphology but different mechanical properties that mimic those of organs most affected by metastasis: liver, bone and lung. Modulation of the mechanical properties was achieved by proper selection of the polymer constituent of the fibers, namely poly(ε-caprolactone) (PCL), gelatin (Gel), a blend of PCL and Gel and the same bland doped with nanoscale hydroxyapatite. Nanofibrous membranes were prepared by electrospinning technique and characterized in terms of morphology and mechanical properties. Cells derived from primary pancreatic tumors were seeded on the constructs and their colonization, morphology, and viability was assessed overtime. Hybrid polymer/lipid nanoparticles were then designed and characterized and their behavior in culture with cells seeded on the different constructs was examined to evaluate whether the interaction between therapeutic carriers and target cells may depend on the mechanical properties of the tissue.