Antioxidant cerium ions-containing mesoporous bioactive glass ultrasmall nanoparticles: Structural, physico-chemical, catalase-mimic and biological properties
Graphical abstract
Introduction
Inflammation after biomaterial implantation can lead to increased levels of reactive oxygen species (ROS). Uncontrolled accumulation of ROS in cells and tissues can cause persistent inflammation and may hamper the tissue regeneration process [1]. Therefore, biomaterials with antioxidant properties are currently being developed in order to control levels of ROS and modulate the inflammatory response [2]. Interestingly, nanoceria (CeO2 nanoparticles) have been found to exhibit antioxidant properties similar to biological antioxidants such as catalase enzyme [3]. The antioxidant effect of nanoceria originates from the co-existence of Ce3+ and Ce4+ oxidation states at the nanoceria surface and the reversible switching (Ce3+↔ Ce4+) between these two oxidation states [3]. Actually, nanoceria possess multifunctional biological properties including antioxidant, anti-inflammatory, antibacterial and anticancer effects [4]. In parallel with this, incorporating Ce into bioactive glass is gaining an increasing interest in bone regeneration and skin wound healing. Actually, several Ce-containing bioactive glasses [5,6] and mesoporous bioactive glasses [7,8] have been reported. However, very few studies reported Ce-containing mesoporous bioactive glass nanoparticles [9,10]. Indeed, the nanoscale form of Ce-containing mesoporous bioactive glass (especially the ultrasmall nanoparticle size, 16–30 nm, reported for the first time in this work) is highly interesting as it can mimic the size of nanoceria (2–30 nm) and it can be internalized by cells while carrying payloads of therapeutic drugs into their mesopores. Mesoporous bioactive glass nanoparticles (mesoporous BGn) have been prepared by several methods including modified Stöber method [11], micro-emulsion method [12] and modified-sol-gel methods e.g. micro-emulsion assisted sol-gel [9,10] and ultrasound-coupled sol-gel [[13], [14], [15]]. Depending on the synthesis method and type of template, mesoporous BGn have shown to have wide variations in their properties including particle chemical composition, particle size, particle morphology, textural properties, biodegradability, ions release kinetics, bioactivity and biological behavior [[10], [11], [12], [13], [14]].
Herein, Ce2O3 was incorporated into mesoporous BGn (SiO2 – CaO binary glass system) using a facile one-pot ultrasound-assisted sol-gel synthesis. Interestingly, Ce2O3 incorporation exerted a significant influence on the particle size and textural properties of mesoporous BGn. Furthermore, in situ formation of CeO2 nanospheres was detected at the surface and in the amorphous glass matrix of mesoporous Ce-BGn. To this end, herein we report for the first time, novel ultrasmall mesoporous Ce-BGn with large specific surface area, high mesoporosity, excellent catalase-mimic activity, unique capability of releasing Ce ions, remarkable bone-like hydroxyapatite formation and good cyto-biocompatibility.
Section snippets
Materials
Tetraethoxysilane (TEOS, ≥ 99 %), calcium nitrate tetrahydrate (CaNT, ≥ 99 %), cerium nitrate hexahydrate (CeNH, ≥ 99.9 %), polyethylene glycol (PEG, Mn = 10000), ammonium hydroxide (NH4OH, 28 %), methanol anhydrous, tris-hydroxymethyl aminomethane (Tris–buffer), 1 N hydrochloric acid, analytical grad chemicals for simulated body fluid (SBF), phosphate buffered saline (PBS) tablets, sulforhodamine-B (SRB) and trichloroacetic acid (TCA) were all purchased from Sigma-Aldrich and used as-received.
Morphology, composition and particle size of mesoporous Ce-BGn
The particle morphology, average particle size and particle size distribution of 0Ce-BGn, 5Ce-BGn and 10Ce-BGn were evaluated from TEM images (Figs. 1 and S1). TEM images of 0Ce-BGn (Fig. S1A) showed spherical nanoparticles with average particle size around 65 nm. Interestingly, TEM images of 5Ce-BGn (Fig. 1A – B) and 10Ce-BGn and (Fig. 1D - E) revealed ultrasmall nanoparticles with spherical morphology and particle size < 30 nm. The particle size distributions of 0Ce-BGn (Fig. S1 C), 5Ce-BGn (
Conclusions
Novel ultrasmall mesoporous Ce-BGn (< 30 nm) were prepared by a facile one-pot ultrasound-coupled sol-gel method. Interestingly, Ce2O3 incorporation excreted a significant influence on the particle size and textural properties of mesoporous BGn. Furthermore, in situ formation of CeO2 nanospheres (3–6 nm) was detected in the amorphous glass matrix of mesoporous Ce-BGn. Taken together, mesoporous Ce-BGn showed remarkable ability to act as an antioxidant (catalase-mimic) through surface containing
CRediT authorship contribution statement
Ahmed El-Fiqi: Conceptualization, Methodology, Investigation, Data curation, Formal analysis, Validation, Writing - original draft, Writing - review & editing. Rasha Allam: Cytotoxicity experiments, Investigation, Validation, Writing - review & editing. Hae-Won Kim: Conceptualization, Writing - review & editing, Funding acquisition.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
This work was supported in part by National Research Foundation (NRF: GRDC program no 2018K1A4A3A01064257), Republic of Korea.
References (27)
- et al.
Oxidative stress in normal and impaired wound repair
Pharmacol. Res.
(2008) - et al.
Evaluation of the anti-oxidative and ROS scavenging properties of biomaterials coated with epigallocatechin gallate for tissue engineering
Acta Biomater.
(2021) - et al.
Mesoporous bioactive glasses doped with cerium: investigation over enzymatic-like mimetic activities and bioactivity
Ceram. Int.
(2019) - et al.
Cerium (III) and (IV) containing mesoporous glasses/alginate beads for bone regeneration: bioactivity, biocompatibility and reactive oxygen species activity
Mater. Sci. Eng. C
(2019) - et al.
Antioxidant mesoporous Ce-doped bioactive glass nanoparticles with anti-inflammatory and pro-osteogenic activities
Mater. Today Bio
(2020) - et al.
Cerium and gallium containing mesoporous bioactive glass nanoparticles for bone regeneration: bioactivity, biocompatibility and antibacterial activity
Mater. Sci. Eng. C
(2021) - et al.
Novel bone-mimetic nanohydroxyapatite/collagen porous scaffolds biomimetically mineralized from surface silanized mesoporous nanobioglass/collagen hybrid scaffold: physicochemical, mechanical and in vivo evaluations
Mater. Sci. Eng. C
(2020) - et al.
Facile and rapid ultrasound-mediated synthesis of spherical mesoporous silica submicron particles with high surface area and worm-like mesoporosity
Mater. Lett.
(2020) - et al.
Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells
Toxicol. Lett.
(2018) - et al.
Iron ions-releasing mesoporous bioactive glass ultrasmall nanoparticles designed as ferroptosis-based bone cancer nanotherapeutics: ultrasonic-coupled sol–gel synthesis, properties and iron ions release
Mater. Lett.
(2021)
Cerium speciation in silicate glasses: structure-property relationships
J. Non-Cryst. Solids
Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications
NPG Asia Mater.
Biomedical applications of nanoceria: new roles for an old player
Nanomedicine
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