Cytotoxicity towards Breast Cancer Cells of Pluronic F-127/Hyaluronic Acid Hydrogel Containing Nitric Oxide Donor and Silica Nanoparticles Loaded with Cisplatin.

The incorporation of both nitric oxide (NO) donor (S-nitrosoglutathione, GSNO) and silica nanoparticles loaded with cisplatin (SiO 2 @CisPt NPs) into a polymeric matrix represents a suitable approach to creating a drug-delivery system with sustained and localized drug release against tumor cells. Herein, we report the synthesis, characterization, and cytotoxicity evaluation of Pluronic F-127/hyaluronic acid hydrogel containing GSNO and SiO 2 @CisPt NPs against breast cancer cells. SiO 2 @CisPt NPs were successfully synthesized, revealing a spherical morphology with an average size of 158 ± 20 nm. Both GSNO and SiO 2 @CisPt NPs were incorporated into the thermoresponsive Pluronic/hyaluronic hydrogel for sustained and localized release of both NO and cisplatin. The kinetics of NO release from a hydrogel matrix revealed spontaneous and sustained release of NO at the millimolar range for 24 h. The MTT assay showed concentration-dependent cytotoxicity of the hydrogel. The combination of GSNO and SiO 2 @CisPt incorporated into a polymeric matrix decreased the cell viability 20% more than the hydrogel containing only GSNO or SiO 2 @CisPt. At 200 µg/mL, this combination led to a critical cell viability of 30%, indicating a synergistic effect between GSNO and SiO 2 @CisPt NPs in the hydrogel matrix, and, therefore, highlighting the potential application of this drug-delivery system in the field of biomedicine.