Genistein-based reactive oxygen species-responsive nanomaterial site-specifically relieves the intestinal toxicity of endocrine-disrupting chemicals.

Endocrine-disrupting chemicals (EDCs) can disrupt the gastrointestinal endocrine system and induce oxidative stress, which eventually leads to intestinal toxicity. Genistein (Gen) has a beneficial effect on the physiological functions of the gastrointestinal tract and can alleviate EDCs damage. As an estrogen-like substance, Gen may also synergize the deleterious influence of EDCs. Therefore, the targeting and concentration of Gen must be controlled during its application. In this study, a novel reactive oxygen species (ROS)-responsive nanomaterial (Gen-NM-2) containing Tempol conjugated ß-cyclodextrin and Gen was prepared. The nano-polymer exhibits a uniform rod-like morphology with an average diameter of 833 ± 12 nm and a negative zeta-potential of -20.3 ± 3.7 mV. Gen-NM-2 protected Gen from rapid metabolism in gastrointestinal tract and displayed a strong ROS scavenging ability. In response to high ROS levels, this material can effectively locate the target site and release Gen, which then exerted its effect by reducing the ROS content and regulating the ERß signaling pathway. Owing to its high bioavailability, Gen-NM-2 at relatively low doses can reduce the intestinal cytotoxicity of EDCs, thus providing a basis for the development of EDCs detoxification therapy.