Targeting functionalized nanoparticles towards 2D and 3D colorectal cancer models from cell lines and patient tumor biospecimens in microfluidics systems

Abstract

Cancer is known for its high mortality rates and for treatments which are often related to undesirable secondary effects. Therefore, the development of alternative methods for treating this disease is of paramount significance. Thus, a powerful strategy is the use of multifunctional nanoparticles (NPs), which have been extensively investigated in the recent years. NPs functionalized with ligands are among the most promising therapeutic-based strategies since they enhance the drug targeting towards tumor cells while minimizing adverse effects. Despite its great potential, few NP-based systems have been approved by the Food and Drug Administration (FDA), especially because of the need of new platforms that mimic with high reliability the human body. As a consequence, the present project is intended to evaluate and compare the action of functionalized silica nanoparticles (SiO2NPs) with kinetic stabilizer (zwitterionic group) and tumor driver (folate group) in 2D and 3D cultures based on healthy and tumor human colon cells. These studies will be conducted in static and flow conditions, using an organ-on-a-chip platform, which consists of a microfluidic system incorporating synthetic in vitro tissues to simulate human physiology at the tissue and organ levels. Subsequently, experiments will be performed using patient colorectal tumor tissues in static and flow conditions, which provides a more reliable analysis on the behavior of NPs in tumors, opening doors for the advancement of personalized medicine.