Yazar "Ur Rehman, Tanzeel" seçeneğine göre listele

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    Development of a histotripsy agent using host-guest interaction
    (İstanbul Medipol Üniversitesi Fen Bilimleri Enstitüsü, 2017) Ur Rehman, Tanzeel; Yüksel Durmaz, Yasemin
    Histotripsy is a mechanical cell ablation technique, which works on the mechanism of acoustic cavitation using microsecond-long, high-frequency ultrasound (US) pulses that can generate a bubble cloud (cavitation) using the already existing gas pockets in the tissue. Once the bubble cloud gains enough energy, it collapses resulting in the cellular destruction/ablation of the surrounding tissue. Histotripsy requires extremely high pressures to initiate cavitation in the tissue. Recently developed Nanodroplet Mediated Histotripsy (NMH) addresses this limitation by lowering the cavitation threshold using perfluorocarbon filled nanodroplets as a histotripsy agent. Despite the fact that these nanodroplets work perfectly for NMH, the synthesis of these nanodroplets is complex, and requires expertise in the eld of polymer chemistry. Thus, this work aims to address the need for a new histotripsy agent that can work as e ectively as nanodroplets, but have better potential in terms of being more user-friendly, straightforward, and economical. Two currently available Food and Drug Administration (FDA) approved and commercial compounds, -cyclodextrin (BCD) and perfluorohexane (PFH), were used to obtain an inclusion complex (IC) through host-guest interaction, where hydrophobic cavity of BCD accommodates hydrophobic perfluorocarbon that might act as cavitation nuclei, and lower the threshold during histotripsy treatment. PFH was successfully encapsulated in the cavity of BCD with an encapsulation efficiency of 98%. Physiochemical characterization of the IC supported the complex formation and indicated the potential of having more than one PFC in the cavity, depending on PFH/BCD ratio. The size of the complex was measured at 48 nm, which is smaller than the size of nanodroplets. However, it has a tendency to form a bigger self-assembly depending on the dispersion concentration, which may affect cavitation behavior. Hemolytic activity and cytotoxicity experiments revealed that the inclusion complex is biocompatible at the concentration as high as 1 mg/mL. Finally, the ability to lower cavitation threshold for histotripsy was tested, and it showed that it acts as desired nuclei sites for cavitation at low pressures of around 15 MPa, indicating that this new agent can be effectively used as a histotripsy agent.
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    Nanoparticle-mediated histotripsy (NMH) using perfluorohexane 'nanocones'
    (Institute of Physics Publishing, 2019) Khirallah, Jennifer; Schmieley, Rebecca; Demirel, Erhan; Ur Rehman, Tanzeel; Howell, Justin; Yüksel Durmaz, Yasemin; Vlaisavljevich, Eli
    Nanoparticle-mediated histotripsy (NMH) is an ultrasound treatment strategy that combines acoustically sensitive nanoparticles with histotripsy. Previous NMH studies using perfluorocarbon (PFC) nanodroplets (ND's), ?200 nm in diameter, demonstrated that NMH can selectively generate cavitation by reducing the cavitation threshold from ?25-30 MPa to ?10-15 MPa. Recent studies have also shown that cavitation nucleation in NMH is directly caused by the incident negative pressure (p-) exposed to the PFC, as predicted by classical nucleation theory (CNT), suggesting that the NMH cavitation threshold is dependent on the total volume of PFC present in the focal region. In this study, we investigate the use of a newly developed NMH nanoparticle synthesized using an inclusion complex of methylated ?-cyclodextrin and perfluorohexane (PFH). These 'nanocones' (NCs) have advantages compared to previously used ND's due to their smaller size (?50 nm), simple synthesis method, higher stability and information of definite PFH amount carried by the NC. To test the hypothesis that NCs can reduce the NMH cavitation threshold similar to ND's, and that the NMH cavitation threshold is dependent upon the total PFH concentration, tissue phantoms containing concentrations of NCs ranging from 10-5 to 10-10 (ml PFH/ml water) were exposed to single cycle ultrasound pulses using a 500 kHz focused transducer where high speed imaging captured cavitation data. Results showed that NCs significantly reduced the histotripsy cavitation threshold to 11.0 MPa for a concentration of 10-5 (ml PFH/ml water), with the threshold increasing at lower concentrations. Finally, the ability of NCs to be used for effective NMH ablation was demonstrated in tissue phantoms containing red blood cells (RBCs). Overall, the results of the study support our hypotheses that NCs can be used for effective NMH therapy and that NC concentration has a predictable threshold-reducing effect.