Antioxidant cerium ions-containing mesoporous bioactive glass ultrasmall nanoparticles: Structural, physico-chemical, catalase-mimic and biological properties

https://doi.org/10.1016/j.colsurfb.2021.111932Get rights and content

Highlights

  • Novel ultrasmall mesoporous Ce-BGn were prepared by ultrasound-assisted sol-gel method.

  • CeO2 nanospheres (3–6 nm) were detected in the amorphous matrix of mesoporous Ce-BGn.

  • XPS and UV–vis DRS confirmed the presence of Ce3+/Ce4+ ions in mesoporous Ce-BGn.

  • Ce-BGn showed remarkable ability to act as an antioxidant (catalase-mimic).

  • Ce-BGn demonstrated excellent in vitro bioactivity and good in vitro cyto-biocombatiblity.

Abstract

The multifunctional biological properties of Ce ions including antioxidant, anti-inflammatory, antibacterial and anti-cancer effects are very encouraging for development of Ce-containing biomaterials with therapeutic properties. Herein, novel Ce3+/Ce4+ ions containing mesoporous bioactive glass ultrasmall nanoparticles (Ce-BGn) were prepared by a facile one-pot ultrasound-assisted sol-gel method. Interestingly, Ce2O3 incorporation exerted a significant influence on the particle size and textural properties of mesoporous BGn (SiO2 – CaO binary glass system). Ce-BGn exhibited ultrasmall nanoparticle size (< 30 nm), mesoporous texture (pore size up to 2.82 nm and pore volume up to 0.191 cm3/g) and large specific surface area ca. 132.9 m2/g. Notably, in situ formation of CeO2 nanospheres (3–6 nm) was detected at the surface and in the amorphous glass matrix of mesoporous Ce-BGn. Importantly, X-ray photoelectron spectroscopy (XPS) revealed the presence of 72.57 % Ce3+ and 27.43 % Ce4+ at the surface of mesoporous Ce-BGn with Ce3+/Ce4+ ratio = 2.66. Furthermore, mesoporous Ce-BGn exhibited high catalase-mimic activity and showed sustained release of Ce (2.5–32 ppm), Ca (85–327 ppm) and Si (54–200 ppm) ions within 4 weeks along with excellent bone-like hydroxyapatite formation. Finally, the in vitro biological behavior of mesoporous Ce-BGn in cell cultures of human skin fibroblasts (HSF) revealed that mesoporous Ce-BGn (with concentrations up to 300 μg/mL) possess good cyto-biocompatibility. Taken together, novel ultrasmall mesoporous Ce-BGn showed remarkable catalase-mimic activity via surface containing Ce3+/Ce4+ ions which can scavenge ROS (Ce3+↔ Ce4+) and decompose H2O2 molecules into H2O and O2. In addition to that, Ce-BGn demonstrated sustained release of bioactive ions (Ce, Ca and Si), excellent bone-like hydroxyapatite formation and good cyto-biocompatibility.

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.

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