Nanocomposite based on Gd2O3 nanoparticles and drug 5-fluorouracil as potential theranostic nano-cargo system

Jaroslava Szűcsová; Adriana Zeleňáková; Eva Beňová; Ľuboš Nagy; Martin Orendáč; Veronika Huntošová; Mária Šoltésová; Jaroslav Kohout; Vít Herynek; Vladimír Zeleňák

doi:10.1016/j.heliyon.2023.e20975

Nanocomposite based on Gd₂O₃ nanoparticles and drug 5-fluorouracil as potential theranostic nano-cargo system

Heliyon. 2023 Oct 14;9(11):e20975. doi: 10.1016/j.heliyon.2023.e20975. eCollection 2023 Nov.

Authors

Affiliations

¹ Institute of Physics, P. J. Šafárik University, Park Angelinum 9, 040 01 Kosice, Slovakia.
² Institute of Chemistry, P. J. Šafárik University, Moyzesova 11, 040 01 Kosice, Slovakia.
³ Department of Solid State Engineering, University of Chemistry & Technology, Technická 5, 166 28 Prague, Czech Republic.
⁴ Center for Interdisciplinary Biosciences, P. J. Šafárik University, Jesenná 5, 040 01 Kosice, Slovakia.
⁵ Department of Low Temperature Physics, Faculty of Mathematics and Physics, Charles University, V Holešovičkách 2, 182 00 Prague, Czech Republic.
⁶ First Faculty of Medicine, Charles University, Center for Advanced Preclinical Imaging (CAPI), Salmovská 3, 120 00 Prague, Czech Republic.

Abstract

We have prepared silica matrix with hexagonal symmetry of pores (SBA-15) and loaded it with anticancer drug 5-Fluorouracil (5-FU) to promote it as a drug delivery system. Gd₂O₃ nanoparticles were incorporated into the matrix to enhance nanosystems applicability as contrast agent for MRI, thus enabled this nanocomposite to be used as multifunctional nano-based therapeutic agent. Drug release profile was obtained by UV-VIS spectroscopy, and it indicates the prolongated release of 5-FU during the first hours and the total release after 5 h. The cytotoxicity tests using MTT-assay, fluorescent microscopy, bright-field microscopy, and flow cytometry were carried out using human glioma U87 MG cells and SK BR 3 cells. The nanocomposite with anticancer drug (Gd₂O₃/SBA-15/5FU) showed toxic behaviour towards studied cells, unlike nanocomposite without drug (Gd₂O₃/SBA-15) that was non-toxic. Our drug delivery system was designed to minimalize negative effect of Gd³⁺ ions at magnetic resonance imaging and drug 5-FU on healthy cells due to their encapsulation into biocompatible silica matrix, so the Gd³⁺ ions are more stable (in comparison to chelates), lower therapeutic dose of 5-FU is needed and its prolongated release from silica pores was confirmed. Very good T1 contrast in MR images was observed even at low concentrations, thus this nanosystem can be potentially used as contrast imaging agent.

Keywords: 5-Fluorouracil; Gd2O3 nanoparticles; MRI; drug delivery; mesoporous silica.