טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentZukerman Hila
SubjectTargeting Multi-Functional Nano-Carriers to Vasoconstricted
Blood Vessels under High Wall Shear Stress
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Netanel Korin
Professor Emeritus Noah Lotan
Full Thesis textFull thesis text - English Version


Abstract

Cardiovascular diseases are among the leading causes of mortality in the world. A serious complication associated with cardiovascular diseases is vasospasm - the narrowing of an artery caused by a persistent smooth muscle contraction. Current therapies include systemic medications and surgical procedures, both being associated with undesired side-effects. To avoid them, this research relies on nano-medicine technologies and implementing them by also taking into account the hemodynamic conditions prevailing at the intended site of action. To this aim, we design and studied multi-functional nanoparticles carriers decorated with specific antibodies as targeting elements and with a specific enzyme as the therapeutic component.  The targeting performance of the functionalized nanoparticles under flow was investigated experimentally using a microfluidic device lined with activated endothelial cells, known to exist in arterial vaso-spasms. Using time-lapse confocal microscopy, we monitored the nanoparticles adhesion under different relevant shear stresses (40-300 dyne/cm2). Results of these experiments showed a higher specific adhesion of the functionalized nanoparticles to activated endothelial cells at all of the examined shear stresses. Moreover, we show that design parameters, such as the coating type and coating density, play a key role in optimizing the adhesion of the nanoparticles under high shear flow. Thus, our results emphasize the need for designing cardiovascular nano-medicines while taking into account hemodynamic considerations.