Co-delivery of curcumin and chrysin through pH-sensitive hyaluronan-modified hollow mesoporous silica nanoparticles for enhanced synergistic anticancer efficiency against thyroid cancer cells

In this work, curcumin (Curc) and chrysin (Chry), two natural anti-cancer agents, are co-loaded into hollow mesoporous silica nanoparticles (HMSNs-SS-HA)-based drug delivery vehicle to target thyroid cancer cells by applying S-S bonds as redox-sensitive linkers and hyaluronic acid (HA) as both capping and targeting agent. Well-dispersed HMSNs-SS-HA are prepared with the size less than 200 nm. Detailed chemo-physical characterizations of the synthesized HMSNs-SS-HA were carried out by using FE-SEM, TEM, FTIR, TGA, DLS and BET. In vitro drug release assay exhibited a controlled and pH responsive behaviour in the presence of GSH and HAase at pHs 7.4 and 5.0. Targeting ability and distribution of Curc/Chry@HMSNs-SS-HA in CD44-positive TPC-1 human papillary thyroid carcinoma cells was demonstrated by laser scanning confocal microscopy. Besides, Curc/Chry@HMSNs-SS-HA exhibited higher synergistic cytotoxicity effect and apoptosis rate compared to single-drug loaded HMSNs-SS-HA and free Curc/Chry combination against TPC-1 cells. Western blotting results also demonstrated a substantial alteration in the expression levels of autophagy-related markers and decrease of p-AKT/AKT and p-mTOR/mTOR ratios in the cells treated with Curc/Chry@HMSNs-SS-HA. Taken together, our research provides the potential of HMSNs-SS-HA as an efficient nanoparticle-based triggered and targeted drug delivery system for co-delivery of Curc and Chry against thyroid cancer cells.