Genistein-based reactive oxygen species-responsive nanomaterial site-specifically relieves the intestinal toxicity of endocrine-disrupting chemicals.
Genistein-based reactive oxygen species-responsive nanomaterial site-specifically relieves the intestinal toxicity of endocrine-disrupting chemicals.
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DOI：
10.1016/j.ijpharm.2022.121478
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发表时间：
2022-01
影响因子：
5.8
通讯作者：
Wentao Fan;Shuhui Liu;Yuting Wu;Xiuyun Cao;Tao Lu;Chaobo Huang;Xizhi Shi;Suquan Song
中科院分区：
文献类型：
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作者：
Wentao Fan;Shuhui Liu;Yuting Wu;Xiuyun Cao;Tao Lu;Chaobo Huang;Xizhi Shi;Suquan Song
内分泌干扰物（EDCs）可干扰胃肠道内分泌系统，诱导氧化应激，最终导致肠道毒性。染料木黄酮（Genistein，Gen）对胃肠道的生理功能有良好的作用，可减轻内分泌干扰物（EDCs）的损伤。作为一种雌激素样物质，Gen也可以协同内分泌干扰物的有害影响。因此，在应用过程中必须控制Gen的靶向性和浓度。本研究制备了一种新型的活性氧响应纳米材料（Gen-NM-2），该材料含有Tempol结合的β-环糊精和Gen。纳米聚合物呈现出均匀的棒状形态，平均直径为833 ± 12 nm，负zeta电位为−20.3 ± 3.7 mV。Gen-NM-2保护Gen免受胃肠道快速代谢的影响，并显示出较强的ROS清除能力。当ROS水平升高时，该材料可有效定位靶位点并释放Gen，通过降低ROS含量和调节ERβ信号通路发挥作用。由于其生物利用度高，Gen-NM-2在相对低的剂量下可以降低内分泌干扰物的肠道细胞毒性，从而为开发内分泌干扰物解毒疗法提供了基础。
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 β-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 ERβ 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.