Fe 3 O 4 nanoparticles for complex targeted delivery and boron neutron capture therapy

Abstract

Magnetic Fe 3 O 4 nanoparticles (NPs) and their surface modification with therapeutic substances are of great interest, especially drug delivery for cancer therapy, including boron-neutron capture therapy (BNCT). In this paper, we present the results of boron-rich compound (carborane borate) attachment to previously aminated by (3-aminopropyl)-trimethoxysilane (APTMS) iron oxide NPs. Fourier transform infrared spectroscopy with Attenuated total reflectance accessory (ATR-FTIR) and energy-dispersive X-ray analysis confirmed the change of the element content of NPs after modification and formation of new bonds between Fe3O4 NPs and the attached molecules. Transmission (TEM) and scanning electron microscopy (SEM) showed Fe3O4 NPs’ average size of 18.9 nm. Phase parameters were studied by powder X-ray diffraction (XRD), and the magnetic behavior of Fe 3 O 4 NPs was elucidated by Mössbauer spectroscopy. The colloidal and chemical stability of NPs was studied using simulated body fluid (phosphate buffer-PBS). Modified NPs have shown excellent stability in PBS (pH = 7.4), characterized by XRD, Mössbauer spectroscopy, and dynamic light scattering (DLS). Biocompatibility was evaluated in-vitro using cultured mouse embryonic fibroblasts (MEFs). The results show us an increasing of IC50 from 0.110 mg/mL for Fe 3 O 4 NPs to 0.405 mg/mL for Fe 3 O 4 -Carborane NPs. The obtained data confirm the biocompatibility and stability of synthesized NPs and the potential to use them in BNCT. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This study was funded by the Ministry of Education and Science of the Republic of Kazakhstan (grant No AP05130947 “Setting the stage for boron neutron capture therapy of cancer in the Republic of Kazakhstan”) and Nazarbayev University “Social Policy Grant” (project title: “Research and development of the new Nano-Optical Sensor based on Polymer Optical Fiber for Near-Field Scanning Optical Microscopy”, PI: Kanat Dukenbayev). The authors also gratefully acknowledge the financial support of the Ministry of Education and Science of the Russian Federation in the framework of Increase Competitiveness Program of NUST «MISiS» (NoK4-2018-036, P02-2017-2-4), implemented by a governmental degree dated 16th of March 2013, No 211. The work was partially supported by Act 211 Government of the Russian Federation, contract No 02.A03.21.0011. This work was partially supported by the Ministry of Education and Science of the Russian Federation (Government task in SUSU 5.5523.2017/8.9)