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Thymoquinone Glucuronide Conjugated Magnetic Nanoparticle for Bimodal Imaging and Treatment of Cancer as a Novel Theranostic Platform

[ Vol. 14 , Issue. 1 ]

Author(s):

İskender İnce*, Zümrüt Biber Müftüler, E.İlker Medine, Özge Kozguş Güldü, Gökhan Takan, Ayşegül Ergönül, Yasemin Parlak, Yeliz Yıldırım, Burcu Çakar, Elvan Sayit Bilgin, Ömer Aras, Erdem Göker and Perihan Ünak*   Pages 23 - 36 ( 14 )

Abstract:


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 cancerous 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 therapy.

Methods: A glucuronide derivative of thymoquinone (TQG) was enzymatically synthesized and conjugated with the synthesized MNP and then radioiodinated with 131I. New Zealand white rabbits 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.

Keywords:

Thymoquinone, thymoquinone glucuronide, magnetic nanoparticles, lung cancer, iodine-131, SPECT, MRI, theranostics.

Affiliation:

Ege University, Department of Nuclear Application, Institute of Nuclear Sciences, Izmir, Ege University, Department of Nuclear Application, Institute of Nuclear Sciences, Izmir, Ege University, Department of Nuclear Application, Institute of Nuclear Sciences, Izmir, Ege University, Department of Nuclear Application, Institute of Nuclear Sciences, Izmir, Ege University, Department of Nuclear Application, Institute of Nuclear Sciences, Izmir, Ege University, Faculty of Medicine Department of Chest Surgery, Izmir, Celal Bayar University, Faculty of Medicine Department of Nuclear Medicine, Manisa, Ege University, Center for Drug R&D and Pharmacokinetic Applications (ARGEFAR), Izmir, Ege University Faculty of Medicine, Division of Medical Oncology, Izmir, Celal Bayar University, Faculty of Medicine Department of Nuclear Medicine, Manisa, Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, Ege University Faculty of Medicine, Division of Medical Oncology, Izmir, Ege University, Department of Nuclear Application, Institute of Nuclear Sciences, Izmir

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