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

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.

Automated summary

This study aimed to develop a tool for imaging and treating lung cancer by utilizing enzymatic release of thymoquinone derivative TQG from glucuronide. Through conjugation with magnetic nanoparticles (MNP) and radioiodination with 131I, positive results were observed in SPECT and MRI studies in rabbits and tumor modeling studies in mice. The findings suggest that TQGMNP could potentially be used for multimodality imaging and treatment of various cancers.