# The Protective Effect of Quercetin on Hydrogen Peroxide-Induced Oxidative Damage in Caco-2 Cells Is Enhanced by Its Loading in Mesoporous Silica Nanoparticles

## TL;DR

Quercetin's ability to protect cells from oxidative damage is improved when it is loaded into mesoporous silica nanoparticles.

## Contribution

The study demonstrates that loading quercetin into mesoporous silica nanoparticles enhances its cytoprotective effect against oxidative stress in Caco-2 cells.

## Key findings

- Quercetin-loaded mesoporous silica nanoparticles showed higher cell viability than free quercetin under oxidative stress.
- Carboxylated mesoporous silica nanoparticles enhanced quercetin uptake into cells.
- Aminated mesoporous silica nanoparticles had the highest quercetin loading capacity.

## Abstract

Background: Quercetin (Q) can reduce cellular oxidative stress, though it is susceptible to degradation in physiological conditions. Through adsorption and protection of Q, mesoporous silica nanoparticles (MSNs) could enhance its bioactivity. This work aimed to determine the effect of Q loading in MSN and in its aminated (A-MSN), carboxylated (C-MSN) or thiolated (T-MSN) derivatives on its Caco-2-cytoprotective effect against H2O2-induced oxidative stress. Methods: The mesoporous silica materials were characterized (FT-IR, ζ-potential, TGA), and their cytotoxicity was assessed; then, they were loaded with Q and incubated with Caco-2 cells prior to oxidative stress induction, and the cytoprotective effect was evaluated through measurement of cell viability. Results: None of the nanoparticles showed toxicity to Caco-2 cells. A-MSN showed the highest Q loading capacity (5.26% ± 0.06%), due to hydrogen-bonding interactions. C-MSN clearly enhanced the Q cellular uptake compared to the other nanoparticles. Oxidative stress decreased Caco-2 cell viability, which was prevented by 100 µM free Q after 18 h incubation. In contrast, higher cell viability than in non-stressed cells was observed with the same Q concentration loaded across all nanoparticle types. Conclusions: Despite the high instability of free quercetin under cell culture conditions, it exerted a time-dependent cytoprotective effect against H2O2-induced oxidative stress that was enhanced upon loading into nanoparticles. Prior release of the Q molecule in the medium is ineffective, and the presence of the loaded material is required.