Browsing Theses and Dissertations, Electronic (ETDs) by Author "Aafreen, Safiya"
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ItemPEG Mediated Fusion Provides Optimum Hybrid Vesicles for in vivo Theragnostic Applications(Johns Hopkins University, 2022-05-06) Aafreen, Safiya; Liu, Guanshu; Xu, Jiadi; Thomas, AlineExtracellular vesicles (EVs) have recently been recognised of possessing a myriad of functions beneficial to disease diagnosis and palliation. Due to their inherent biological characteristics, immunotolerance and ubiquitous prevalence in biological fluids and tissues they outperform liposomes as therapeutic carriers and imaging probes. Though EVs were first discovered four decades ago, there are several hurdles to their translation and use. Standardisation of their isolation and characterisation has not been established owing to the large degree of heterogeneity in this class of biological vesicles. Furthermore, as these vesicles are secreted from cells, there is a constraint in the modification and loading of these particles, relative to synthetic liposomes, that can be implemented without compromising membrane integrity and their inherent organotropism. Thereby, methods to merge the advantages conferred by both systems (liposomes and EVs) is highly lucrative and has been attempted by various groups to produce hybrid vesicles from freeze-thawing, extrusion, or incubation protocols. The work in this thesis is the result of an attempt to create a particle that is more conducive to theragnostic research by quantitatively comparing prevailing strategies of fusing liposomes and EV particles. The first chapter provides insight into EV biogenesis, their biological roles, their modulation strategies, and their applications as therapeutics and as probes for in vivo imaging techniques. The second chapter assesses different fusion strategies by analysing Nanoparticle Tracking Analysis, Förster resonance energy transfer, fluorescence, and magnetic particle imaging of the formed hybrid vesicles. The third chapter details data obtained from the experiments and subsequent in vivo theragnostic investigations conducted of ameliorating Multiple Sclerosis and radiation-induced brain injury. The work in this thesis provides preliminary evidence that the PEG-mediated fusion strategy, developed by the Liu group, is the superior fusion technique for preserving membrane integrity and cargo.