Nanoparticles and drug eluting stents for disease detection and treatment.

摘要

This thesis presents the results of experimental and theoretical studies of nanoparticle entry/adhesion to breast cancer cells and adhesion in drug-eluting stents. Atomic Force Microscopy (AFM) techniques are used to quantify the adhesion. The thermodynamics and kinetics concepts are presented for the modeling of nanoparticle entry into breast cancer cells. In the case of the drug-eluting stents studies, a combination of adhesion theory and fracture mechanics concepts is used to estimate the adhesion energies.;To investigate the specific accumulation of the functionalized super-paramagnetic iron oxide nanoparticles (SPIONs) in breast cancer cells, a combination of transmission electron microscopy (TEM) and spectrophotometric analysis was used. It is shown that SPIONs conjugated to luteinizing hormone releasing hormone (LHRH) (LHRH-SPIONs), can be used to specifically target breast cancer cells. They also act as contrast enhancement agents during the magnetic resonance imaging (MRI) of breast cancer xenografts.;The adhesion between LHRH and breast cancer cells is an important factor for LHRH-SPIONs to target breast cancer cells. AFM techniques were used to quantify adhesion between LHRH peptides and their receptors on breast cancer cells. The adhesion force between LHRH-coated AFM tips and human breast cancer cells is shown to be about five times greater than that between LHRH-coated AFM tips and normal breast cells. This result also suggests that force microscopy can be used for the specific detection of breast cancer cells.;Adhesion and fracture mechanics techniques were used to study the adhesion between the drug eluting layer and Parylene C layer coated onto a model drug-eluting stent. AFM force--displacement measurements were used to quantify the adhesion between the parylene C primer and the drug-eluting layer and the cohesion between the three constituents of the drug-eluting layer. Adhesion theories were then used to relate the measured forces to adhesion energies. Brazil nut sandwich specimens, with initial cracks at the parylene/drug interface, were used to measure the interfacial fracture energy between Parylene C and drug layer at different mode mixities. The adhesion energies obtained from the AFM measurements were shown to be consistent with mode I interfacial fracture toughness that were obtained from fracture tests.