Fe₃O₄ Nanoparticles for Complex Targeted Delivery and Boron Neutron Capture Therapy.

Kanat Dukenbayev,Elena Shumskaya,Yevgeniy Gorin,Denis Vinnik,Marina Anisovich,Sergey Trukhanov,Ilya Korolkov,Maxim Zdorovets,Daria Tishkevich,Daniele Tosi,Egor Kaniukov,Alex Trukhanov,Artem Kozlovskiy,Carlo Molardi

doi:10.3390/nano9040494

Abstract

Magnetic Fe3O4 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 Fe3O4 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 Fe3O4 NPs to 0.405 mg/mL for Fe3O4-Carborane NPs. The obtained data confirm the biocompatibility and stability of synthesized NPs and the potential to use them in BNCT.

Highlights

Magnetic iron oxide nanoparticles (NPs), such as magnetite (Fe3O4) and maghemite (γ-Fe2O3), have been found and applied in a wide range of biomedical applications [1,2,3,4,5,6,7,8,9], including magnetic resonance imaging, magnetic hyperthermia, cancer therapy, and drug delivery; they find applications in catalysis [10,11,12] and in magnetic separation [13,14]
The application of iron oxide NPs in medicine reveals one more issue: An intravenous delivery agent should be eliminated from the blood and not cause accumulation in the organism, which can lead to side effects
Zang et al [17] reported that the accumulation and elimination of iron oxide NPs were found on a sample of zebrafish, and as a result, magnetic nanoparticles were eliminated from 86% to 100% by 24 days

Summary

Introduction

Magnetic iron oxide nanoparticles (NPs), such as magnetite (Fe3O4) and maghemite (γ-Fe2O3), have been found and applied in a wide range of biomedical applications [1,2,3,4,5,6,7,8,9], including magnetic resonance imaging, magnetic hyperthermia, cancer therapy, and drug delivery; they find applications in catalysis [10,11,12] and in magnetic separation [13,14]. Weissleder et al [18] studied the toxic effect on rats and beagle dogs, revealing that no toxicity was detected in animals that received 3000 mmol Fe/kg overall Various materials, such as silane-based compounds, metals, polymers, and fatty and amino acids, have been used for coating and stabilizing the surface of iron oxide NPs in order to reduce toxicity and increase biocompatibility [19,20,21]. The modification of iron oxide NPs by silanes with functional groups can lead to an easy attachment of payloads. One of these payloads can be a boron-rich compound for potential use as drug in boron neutron capture therapy of cancer (BNCT)

Methods

Results

Conclusion