Synthesis of Gd-DTPA Carborane-Containing Compound and Its Immobilization on Iron Oxide Nanoparticles for Potential Application in Neutron Capture Therapy
Korolkov I.V. Zaboronok A. Izbasar K.A. Bekbol Z.A. Lissovskaya L.I. Zibert A.V. Shakirzyanov R.I. Korganbayeva L.N. Yang H. Ishikawa E. Zdorovets M.V.
June 2024Multidisciplinary Digital Publishing Institute (MDPI)
Pharmaceutics
2024#16Issue 6
Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting.
carborane , drug delivery , Gd-DTPA , iron oxide , nanoparticles , neutron capture therapy
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The Institute of Nuclear Physics, Ibragimov Str. 1, Almaty, 050032, Kazakhstan
Engineering Profile Laboratory, L.N. Gumilyov, Eurasian National University, Satpaev Str. 5, Astana, 010008, Kazakhstan
Department of Neurosurgery, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan
The Institute of Nuclear Physics
Engineering Profile Laboratory
Department of Neurosurgery
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