Targeted co-delivery of myricetin and doxorubicin through folic acid functionalized mesoporous silica nanoparticles

Abstract In this study, we developed a folic acid-functionalized mesoporous silica nanoparticle to deliver doxorubicin with the antioxidant myricetin to reduce drug toxicity. The nanoparticles were synthesized by the Stöber method and characterized using Fourier-transform infrared spectroscopy for identifying functional groups, x-ray diffraction study confirmed amorphous structure, zeta sizer analysis indicated the size 184 ± 5 nm with zeta potential of +6.21 mV, Scanning and Transmission electron microscopy confirms spherical shape of the nanoparticle. The Brunauer–Emmett–Teller measures surface area and pore volume at 314.410 m 2 g −1 and 0.246 cc g −1 respectively. The loading efficiency for doxorubicin and myricetin was 22.23% and 43.24% respectively and overall entrapment efficiency was 88.97% using UV spectroscopy. The sustained drug release was observed under tumor-mimicking conditions with 82% for doxorubicin and 76% for myricetin tested for 120 h. The Chou–Talalay method confirmed a strong synergistic effect of doxorubicin and myricetin (0.27) enabling a 3.7-fold reduction in the required doxorubicin dose. In in vitro studies, the toxicity of nanoparticles was investigated by cell viability, cytotoxicity, and counter-stain assays, which showed higher cytotoxicity in A549 and Colo205 cancer cells, but less toxicity was observed in normal L132 cells. then, an apoptosis assay was performed for the nanoparticle using Annexin V, and increased early apoptosis (39.9%) was noticed in A549 cancer cells when compared with free drugs (7%). In conclusion, the cytotoxicity of nanoparticles is reduced in normal cells due to the presence of myricetin, which mitigates oxidative stress by enhancing therapeutic efficacy.