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    Synthesis of radioiodinated thymoquinone glucuronide conjugated magnetic nanoparticle (125I-TQG-Fe3 O4) and its cytotoxicity and in vitro affinity
    (İstanbul Medipol University, 2018) İnce İ.; Biber Müftüler Z.; Medine E.İ.; Güldü Ö.K.; Tekin V.; Aktar S.; Göker E.; Ünak P.
    The aim of the current study is to develop solid, semisolid or liquid form of radionuclide labeled thymoquinone glucuronide conjugated magnetite nanoparticles those targets to the tumor for diagnosis and therapy of cancer. For this purpose, thymoquinone (TQ), a molecule present in the seeds of Nigella (Nigella sativa) used to enhance the affinity of the drug to the tumor cells. TQ was isolated from its microsomes and an enzymatic method applied to synthesize beta glucuronic acid derivatized thymoquinone glucuronide (TQG). TQG attached magnetic nanoparticles (TQG-Fe3 O4). TQG- Fe3 O4 were radiolabeled with 125I and (125I-TQG- Fe3 O4) its cytotoxic effect and in vitro affinity was investigated. The IC50 values of TQG- Fe3 O4 were found 27.31, 18.68, 11.88 (µg/mL) respectively 24, 48 and 72 hours against A549 cell line by WST-8 test as a colorimetric way. Incorporation ratios of TQG- Fe3 O4 with A549 cells is the highest levels. It is seen that TQG-Fe3O4 could inhibit the apoptosis on A549 cells but, there is no apoptotic effect of the samples on BEAS-2B cells. Size distribution, cellular uptake and toxicity characteristics of TQG- Fe3 O4 in this study maintains a useful targeted delivery system in lung cancer diagnosis and therapy. © 2018, İstanbul Medipol University. All rights reserved.
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    Thymoquinone glucuronide conjugated magnetic nanoparticle for bimo-dal imaging and treatment of cancer as a novel theranostic platform
    (Bentham Science Publishers, 2021) İnce İ.; Müftüler Z.B.; Medine E.İ.; Güldü Ö.K.; Takan G.; Ergönül A.; Aras Ö.
    Background: Theranostic oncology combines therapy and diagnosis and is a new field of medicine that specifically targets the disease by using targeted molecules to destroy the cancer-ous cells without damaging the surrounding healthy tissues. Objective: We aimed to develop a tool that exploits enzymatic TQ release from glucuronide (G) for the imaging and treatment of lung cancer. We added magnetic nanoparticles (MNP) to enable magnetic hyperthermia and MRI, as well as 131I to enable SPECT imaging and radionuclide thera-py. Methods: A glucuronide derivative of thymoquinone (TQG) was enzymatically synthesized and conjugated with the synthesized MNP and then radioiodinated with 131I. New Zealand white rab-bits were used in SPECT and MRI studies, while tumor modeling studies were performed on 6–7-week-old nude mice utilized with bioluminescence imaging. Results: Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectra confirmed the expected structures of TQG. The dimensions of nanoparticles were below 10 nm and they had rather polyhedral shapes. Nanoparticles were radioiodinated with 131I with over 95% yield. In imaging studies, in xenograft models, tumor volume was significantly reduced in TQGMNP-treated mice but not in non-treated mice. Among mice treated intravenously with TQGMNP, xenograft tumor models disappeared after 10 and 15 days, respectively. Conclusion: Our findings suggest that TQGMNP in solid, semi-solid and liquid formulations can be developed using different radiolabeling nuclides for applications in multimodality imaging (SPECT and MRI). By altering the characteristics of radionuclides, TQGMNP may ultimately be used not only for diagnosis but also for the treatment of various cancers as an in vitro diagnostic kit for the diagnosis of beta glucuronidase-rich cancers. © 2021 Bentham Science Publishers.