A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Cellular senescence(definition) is the results of aging and age-related diseases, and the development of anti-aging methods may improve health and extend longevity. The natural flavonol fisetin has been shown to antagonize senescence <i>in vitro</i> and increases longevity <i>in vivo</i>, but has poor water solubility and limited bioavailability. In this study, a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides (WPI-GOS) Maillard conjugate, which could recognize senescence associated β-galactosidase in senescent cells. The fisetin nanoparticles possessed a high encapsulation efficiency, excellent dispersibility in water, good storage stability and well biocompatibility. Moreover, they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy, and inhibit the oxidative stress-induced cellular senescence <i>in vitro</i>. Thus, this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.