Acute liver failure (ALF) is a severe liver disease with high mortality rate. Inflammasome is a newly-found and promising target for effective treatment of immunity-associated diseases including liver disease, and dopamine has recently been proved as an inhibitor for NLRP3 inflammasome. This work demonstrates a diselenide-based nanodrug for ALF treatment through inhibiting NLRP3 inflammasome activation and enhancing liver regeneration. A diselenide-containing molecule (DSeSeD) has been synthesized via covalently linking two l-Dopa molecules to a diselenide linker, and the resultant molecules form stable nanoparticles in aqueous media and encapsulate SW033291 (an inhibitor of prostaglandin-degrading enzyme that hampers liver regeneration) to produce the nanodrug (SW@DSeSeD). As a nanoscale prodrug, SW@DSeSeD protects its payloads from decomposition in bloodstream upon administration, accumulates in liver of ALF mice, then responds to the overexpressed ROS and thereby releases SW033291 as well as a stable dopamine precursor that can transform into dopamine in hepatic cells, thus achieving significant therapeutic efficacy against ALF through inhibiting NLRP3 inflammasome activation and enhancing hepatic regeneration. Moreover, multiple contrast agents have been loaded onto the nanodrug to achieve fluorescence, optoacoustic and magnetic resonance imaging for nanodrug location and disease evaluation.

急性肝衰竭（ALF）是一种严重的肝病，死亡率很高。炎性小体是有效治疗与免疫相关的疾病（包括肝脏疾病）的新发现的有希望的靶标，最近多巴胺已被证明是NLRP3炎性小体的抑制剂。这项工作证明了通过抑制NLRP3炎性小体激活并增强肝脏再生，可用于ALF治疗的基于二硒化物的纳米药物。将含有二硒化物分子（DSeSeD）已经经由共价连接两个被合成升-将多巴分子连接至二硒化物连接体，所得分子在水性介质中形成稳定的纳米颗粒，并包裹SW033291（阻碍肝脏再生的前列腺素降解酶抑制剂）以生产纳米药物（SW @ DSeSeD）。作为一种纳米级前药，SW @ DSeSeD可以保护其有效载荷免于给药后在血流中分解，在ALF小鼠的肝脏中积累，然后对过表达的ROS作出反应，从而释放出SW033291以及稳定的多巴胺前体，后者可以在肝细胞中转化为多巴胺因此，通过抑制NLRP3炎性小体激活并增强肝再生，可实现针对ALF的显着治疗效果。此外，多种造影剂已加载到纳米药物上以实现荧光，