Kanber, Mohammad2023-06-052023-052023-05-03May 2023http://hdl.handle.net/10342/12880Cancer treatment is one of the major health problems that burdens society. According to the latest publication of the American Cancer Society, the cancer mortality rate has reached 32% in 2022 in the US. To address these alarming numbers, some gold standards, including therapeutic targeting, are being used to treat cancer. However, when tumor grows beyond a critical size, its vascular system differentiates abnormally and erratically creating heterogeneous endothelial barriers that further restricts drug deliveries into tumors. One way to overcome this problem is to induce endothelial leakiness using nanoparticles (NanoEL), so therapeutic drugs can be successfully delivered. While several methods exist, none has been established as a valid clinical approach. The most concerning complication is related to the fact that uncontrolled NanoEL prompts subsequent tumor migration and the appearance of new metastatic sites. In this research, we propose a new non-invasive approach based on magneto-mechanical actuation to remotely control the NanoEL by implementing PEGylated superparamagnetic iron oxide nanoparticles (PEG SPIONs), which are actuated by non-heating super low-frequency magnetic fields. As proof of concept, we developed a 2D cell culture model based on human umbilical vein endothelial cells (HUVEC). Our findings indicate that PEG-SPIONs can assemble within the actin filaments. When magnetically actuated, magnetic forces are translated into mechanical agitation, which induced actin remodeling and subsequent disruption of VE-cadherin junctions. This enabled us to deliver therapeutic drugs across the endothelium in a controlled manner. This approach has the potential to avert cancer migration and provides a remotely controlled drug delivery method harnessing the physics and biology of endothelial adherens junctions. This approach can open up new avenues for targeted drug delivery into anatomic regions within the body for a broad range of disease interventions.application/pdfenEndothelium leakiness, magnetic field, magnetic nanoparticles, magneto-mechanical actuation.Master's Thesis2023-06-02