Antioxidant potential and biocompatibility of pomegranate peel extract functionalized silica nanoparticles

Abstract: The pomegranate peel extract (PPE) is an agri-food waste rich in bioactive molecules, with antioxidant, antimicrobial and anticancer properties, but its potential is limited by oxidative degradation from heat and light sensitivity. Herein, pomegranate peel extract-silica hybrid nanoparticles (MSNs@PPE) were synthesized via a sol-gel wet chemical approach, where pomegranate peel extract (PPE) was physically adsorbed onto mesoporous silica nanoparticles (MSNs) previously functionalized with (3-aminopropyl) triethoxysilane (APTS). Two hybrid nanoparticles, MSNs@PPE 2 (2:1 weight ratio) and MSNs@PPE 1 (1:1 weight ratio), were developed, with MSNs@PPE 2 and MSNs@PPE 1 showing PPE encapsulation of ~95% and ~70%, respectively. TEM microscopy showed ~90 nm monodispersed nanoparticles, with slight increase at higher PPE content. FT-IR confirmed successful functionalization and PPE adsorption, while DLS/ζ-potential showed stable dispersion. MTT assay, cytofluorimetric analysis, and immunofluorescence microscopy evaluated cytotoxicity, cellular uptake, and apoptosis in L929 cells. MSNs@PPE revealed significant and long-term antioxidant stability, high cellular uptake, and no cytotoxic effects, also preventing H₂O₂-induced oxidative stress, when administered at 50 µg/ml. At 100 μg/mL, they showed an increase of cytotoxicity and apoptotic events. Hybrid MSNs enhanced the stability, bioavailability, and controlled delivery of PPE polyphenols, emerging as innovative and versatile nanomaterials with potential for biomedical/food applications, in line with circular bioeconomy.