Yazar "Hall, Sarah" seçeneğine göre listele

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  • Küçük Resim
    Öğe
    Bioconjugated beta-cyclodextrin-perfluorohexane nanocone clusters as functional nanoparticles for nanoparticle-mediated histotripsy
    (American Chemical Society, 2022) Toydemir, Cemran; Hall, Sarah; Demirel, Erhan; Elmacı, Dilşah Nur; Göl, Deniz; Vlaisavljevich, Eli; Yüksel Durmaz, Yasemin
    Nanocone clusters (NCCs) are new-generation agents of nanoparticle-mediated histotripsy (NMH) recently developed to address the limitations of previously designed nanodroplets (NDs). NCCs can be obtained by simply mixing FDA-approved cyclodextrins (CD) and suitable perfluorocarbons (PFCs), which result in smaller size aggregates, detectable PFC amount, and more stable long-term storage since the obtained powder can be stored and redispersed as needed. Previous experimental and computational studies showed that NCCs consist of an organization of inclusion complexes of CD and PFC around free PFC droplets, and their aggregate behavior depends on the localization of PFC in the cavity and the water solubility of CD derivatives. It has been shown that beta-cyclodextrin (beta CD) and perfluorohexane (PFH) are ideal candidates for NCCs that can be isolated as a powder with high PFC content among various CD and PFC derivatives. This study focuses on the further development of the selected NCC composition to enhance the potential of NMH therapy while also enabling more detailed future experiments in vitro and in vivo. It is aimed to show the bioconjugation potential of NCCs through the example of the most commonly used functionalization methods such as targeting, PEGylation, and fluorescent labeling. For this purpose, beta CD as a building block was monofunctionalized with groups such as azide, alkyne, and amine groups that allow for effective coupling reactions such as the "click" reaction and N-(3-dimethylaminopropyl)-N '-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling. These monofunctional beta CDs were used as building blocks of NCCs in the presence of PFH to obtain functional NCCs as precursors of bioconjugation. EPPT1 as a synthetic peptide specific to uMUC1 and folic acid (FA) as the most commonly used targeting agent along with PEGylation were successfully shown as bioconjugation examples. Lastly, fluorescently labeled NCCs were obtained via fluorescein isothiocyanate (FITC) and alkyne functional NCC reaction through propargyl amine and isothiocyanate group reaction. The obtained bioconjugates were tested in vitro to validate the conjugation, and the ability to lower the histotripsy cavitation threshold, which is necessary for NMH, was demonstrated for all bioconjugates. Overall, the results showed that all obtained bioconjugates successfully lowered the cavitation threshold pressure while also fulfilling the desired bioconjugation metrics to serve as improved tools to enhance NMH as a targeted noninvasive ablation method.
  • Küçük Resim
    Öğe
    Bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic or artificial cavitation nuclei
    (Elsevier Science Inc, 2021) Edsall, Connor; Khan, Zerin Mahzabin; Mancia, Lauren; Hall, Sarah; Mustafa, Waleed; Johnsen, Eric; Klibanov, Alexander L.; Yüksel Durmaz, Yasemin; Vlaisavljevich, Eli
    The study described here examined the effects of cavitation nuclei characteristics on histotripsy. Highspeed optical imaging was used to compare bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic and artificial cavitation nuclei (gas-filled microbubbles, fluid-filled nanocones). Results showed a significant decrease in the cavitation threshold for microbubbles and nanocones compared with intrinsic-nuclei controls, with predictable and well-defined bubble clouds generated in all cases. Red blood cell experiments showed complete ablations for intrinsic and nanocone phantoms, but only partial ablation in microbubble phantoms. Results also revealed a lower rate of ablation in artificial-nuclei phantoms because of reduced bubble expansion (and corresponding decreases in stress and strain). Overall, this study demonstrates the potential of using artificial nuclei to reduce the histotripsy cavitation threshold while highlighting differences in the bubble cloud behavior and ablation capacity that need to be considered in the future development of these approaches.
  • Küçük Resim
    Öğe
    Experimental and computational investigation of clustering behavior of cyclodextrin-perfluorocarbon inclusion complexes as effective histotripsy agents
    (American Chemical Society, 2022) Kaymaz, Betül; Mustafa, Waleed; Hall, Sarah; Vlaisavljevich, Eli; Şensoy, Özge; Yüksel Durmaz, Yasemin
    Recently developed nanocones (NCs), which are inclusion complexes that are made up of cyclodextrins (CDs) and perfluorocarbons (PFCs), have shown promising results in nanoparticle-mediated histotripsy (NMH) applications due to stable inclusion complexation, PFC quantification, simple synthesis, and processing. FDA-approved ?CD and its modified versions such as low-degree methylated ?CD have been previously demonstrated as prime examples of structures capable of accommodating PFC molecules. However, the complex formation potential of different CDs with various cavity sizes in the presence of PFC molecules, and their consequent aggregation, needs to be explored. In the present study, the complexation and aggregation potential of some natural CDs and their respective derivatives either exposed to perfluoropentane (PFP) or perfluorohexane (PFH) were studied in the wet lab. Computational studies were also performed to account for the limitations faced in PFC quantification because of the low optical density of PFCs within the CD complex and to discover the best candidate for NMH applications. All results revealed that only ?CD and ?CD (except HM?CD) derivatives form an inclusion complex with PFCs and only LM?CD, ?CD, and ?CD form nanocone clusters (NCCs), which precipitate and can be collected for use. Furthermore, the data collectively show that ?CD and PFCs have the best complexation due to stable complex formation, ease of production, and product recovery, especially with PFH as a more suitable candidate due to its high boiling point, which allows workability during synthesis. Although simulations suggest that highly stable inclusion complexes exist, such as HP?CD, the cluster formation resulting in precipitation is hindered due to the high solubility of CDs in water, resulting in intangible yields to work with even after employing general laboratory recovery methods. Conclusively, histotripsy cavitation experiments successfully showed a decreased cavitation threshold among optimal NCC candidates that were identified, supporting their use in NMH.
  • Küçük Resim Yok
    Öğe
    Investigation of optimum production conditions and the stability of ?-cyclodextrin-perfluorocarbon nanocone clusters for histotripsy applications
    (2024) Mustafa, Waleed; Hall, Sarah; Huynh, Laura; Mannasse, Rachel; Lüleburgaz, Serter; Vlaisavljevich, Eli; Yüksel Durmaz, Yasemin
    Nanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ?-cyclodextrin (?CD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ?CD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ?CD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster’s particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.