This dissertation is about design and synthesis of glyconanoparticles for certain in vivo applications including imaging amyloid beta fibrils in Alzheimer’s disease, imaging inflammatory atherosclerotic plaques and inhibition of atherosclerotic plaque inflammation. Amyloid beta (Aβ) accumulation and deposition in the brain tissue are one of the most important hallmarks of Alzheimer’s disease (AD). Therefore, Aβ is an attractive target for imaging AD, however, designing a nanoprobe with the ability to pass through the blood brain barrier (BBB) and reaching Aβ plaques is a significant challenge. The first part of this dissertation covers the synthesis of a glyconanoparticle enabling to pass the BBB and bind with Aβ fibrils. Briefly, synthesis, characterization and application of this glyconanoparticle for magnetic resonance imaging (MRI) of Aβ plaques in a mouse model of AD (B6C3) have been presented. Majority of patients that experience cardiac arrests have atherosclerosis, which is the inflammatory disease of arterial walls and the major cause of heart attacks and strokes. Imaging techniques that can enable detection of atherosclerotic plaques before clinical manifestation are urgently needed. CD44 is a cell surface protein overexpressed in the plaque tissues and its expression level is associated with the risk of plaque rupture. The second chapter explains atherosclerosis disease and nanomedicine for targeting inflammatory atherosclerotic plaques. The third chapter of this dissertation presents the development of hyaluronan (HA) coated iron oxide nanoparticles for active targeting of the plaques. These nanoprobes can not only bind with atherosclerotic plaques through their HA ligands but also function as T2 based MRI contrast agents for plaque diagnosis. Moreover, the effect of nanoprobe morphology on inflammation has been studied indicating that engineering nanoprobe shape could decrease inflammatory responses, which makes it a superior candidate for imaging inflammatory atherosclerotic plaques. Concisely, design and synthesis of HA conjugated nanoworm (HA-NW) have been explained. Then, inflammatory responses to HA conjugated nanoparticles in vitro and in vivo in apoE knockout mouse model have been presented. Finally, the ability of HA-NW for in vivo imaging of atherosclerotic plaques by MRI has been studied.The last part of this dissertation goes over design and synthesis of hyaluronan conjugated atorvastatin nanoparticle (HA-ATV NP). This therapeutic formulation has been designed to deliver ATV to the inflammatory atherosclerotic plaques to reduce plaque inflammation. Then, HA-ATV NP anti-inflammatory effects in vitro and its therapeutic effect in vivo in apoE knockout mouse model have been explained. It has been shown that intravenous administration of this formulation (high dose, 8.5 mg ATV/ kg), every other day for one week can significantly reduce the plaques inflammation.
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