Functionalized Mesoporous Silica as Doxorubicin Carriers and Cytotoxicity Boosters

Abstract

Mesoporous silica nanoparticles (MSNs) bearing methyl, thiol or glucose groups were synthesized, and their encapsulation and release behaviors for the anticancer drug Doxorubicin (Dox) were investigated in comparison with nonporous homologous materials. The chemical modification of thiol-functional silica with a double bond glucoside was completed for the first time, by green thiol-ene photoaddition. The MSNs were characterized in terms of structure (FT-IR, Raman), morphology (TEM), porosity (nitrogen sorption–desorption) and Zeta potential measurements. The physical interactions responsible for the Dox encapsulation were investigated by analytic methods and MD simulations, and were correlated with the high loading efficiency of MSNs with thiol and glucose groups. High release at pH 5 was observed in most cases, with thiol-MSN exhibiting 98.25% cumulative release in sustained profile. At pH 7.4, the glucose-MSN showed 75.4% cumulative release, while the methyl-MSN exhibited a sustained release trend. The in vitro cytotoxicity was evaluated on NDHF, MeWo and HeLa cell lines by CellTiter-Glo assay, revealing strong cytotoxic effects in all of the loaded silica at low equivalent Dox concentration and selectivity for cancer cells. Atypical applications of each MSN as intravaginal, topical or oral Dox administration route could be proposed.

Synthesis and Electrochemical Evaluation of MSNs-PbAE Nanocontainers for the Controlled Release of Caffeine as a Corrosion Inhibitor

“…A peak at 1632 cm −1 attributable to the bends of OH bonds can also be observed [32]. Additionally, there are no peaks located at 2930 cm −1 and 2850 cm −1 , corresponding to the symmetrical and asymmetric tension-type vibrations of methylene groups, respectively, that could indicate the presence of surfactant, so its complete removal is confirmed [21,33].…”

One‐Pot Synthesis of Doxorubicin‐Bioactive Glass‐Ceramic Hybrid Nanoparticles through a Bio‐Inspired Route for Anti‐Cancer Therapy

“…[45][46][47] Peaks at ∼ 790 cm À 1 observed for all DOX-BG ceramic nanoparticles correspond to SiÀ O À symmetric bending and stretching vibrations in the silica ring structure of the bioactive glass and CÀ SÀ C stretching vibrations. [45,47] The band at ∼ 550 cm À 1 corresponds to PÀ O vibrations present due to the interaction of the phosphate group with non-bonding SiÀ O À groups in the bioactive glass-ceramic structure. [15] In case of BG prepared without DOX, the highly intense peaks observed from 1550 to 1400 cm À 1 along with peaks corresponding to SiO 2 (1100 cm À 1 , 956 cm À 1 , 795 cm À 1 ) indicate BG ceramic doped with crystalline carbonated hydroxyapatite [48,49] probably due to longer reaction time (1 week to month) in TRIZMA leading to deposition of carbonated hydroxyapatite nanocrystals on formed BG ceramic particles.FTIR data suggests that the linkage between doxorubicin and bioactive glass-ceramic structure is mainly physical in nature.…”

“…Further, the photo stability of the drug has been reported to improve when present in encapsulated form in pores of silica structure. [45] Thermogravimetric analysis of bioactive glass-ceramic particles with and without DOX depicts different thermograms (Figure 3c). For BG ceramicformulations without DOX, 23 wt/ wt % weight loss could be observed throughout the temperature range.…”

“…[43] In-vitro drug release profile of DOX from DOX-BG ceramicnanoparticles was carried out in acidic buffer adjusted to pH 4.8 as the internalized particles in cells are generally trapped in endosomal or lysosomal pH which is generally acidic in nature. [22,45] It was observed that the DOX-BG ceramicnanoparticles synthesized with increasing DOX concentrations as template could release doxorubicin slowly and steadily within first 24 hours (Figure 6a). In fact, the absolute amount of DOX being highest in 0.75 DOX-BG ceramic nanoparticles (as observed from loading studies) established highest release (∼ 40-48 %) when compared to 0.25 and 0.50 DOX-BG ceramicnanoparticles (10-25 %).…”

“…The period of drug release was observed for 24 h keeping in mind cellular in-vitro studies where cytotoxic effect of the DOX-BG ceramic nanoparticles was observed for 24 h. Higher and sustained drug release profile for DOX-BG ceramic in acidic environment when compared to that at neutral pH can be due to the weakening of the electrostatic interaction of protonated DOX with the ionized silanol in the bioglass structure. [22,27,45,56] Also, DOX is reported to be more stable in acidic environment due to enhanced hydrophilicity which further leads to better release in acidic pH. [23] Further, comparatively slower and steady dissolution of the compact bioactive glass-ceramic matrix in DOX-BG ceramic nanoparticles in presence of acidic pH may contribute to the slow and sustained drug release.…”