Lupus nephritis (LN) is a major cause of morbidity and mortality among systemic lupus erythematosus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GC side effects while maintaining their potent therapeutic efficacy, we have developed a macromolecular prodrug nanomedicine based on dexamethasone (ZSJ-0228). The focus of this study was to investigate its long-term efficacy and, most importantly, safety in the lupus-prone NZB/W F1 mouse. Monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. In contrast to treatment with dose equivalent daily free dexamethasone, long-term monthly ZSJ-0228 did not result in any measurable GC-associated side effects. With its outstanding efficacy and exceptional safety, it is anticipated that ZSJ-0228 may be a novel therapy for long-term clinical management of LN.

狼疮性肾炎 (LN) 是系统性红斑狼疮患者发病率和死亡率的主要原因。糖皮质激素 (GC) 统一用于临床 LN 管理。然而，它们臭名昭著的毒性阻碍了长期的临床应用。为了在保持其有效治疗功效的同时规避 GC 副作用，我们开发了一种基于地塞米松 (ZSJ-0228) 的大分子前药纳米药物。本研究的重点是研究其长期疗效，最重要的是研究狼疮易发 NZB/W F1 小鼠的安全性。五个月的每月 ZSJ-0228 治疗显着降低了 NZB/W F1 小鼠肾炎的发生率，并提高了存活率。与剂量当量的每日游离地塞米松治疗相比，长期每月 ZSJ-0228 未导致任何可测量的 GC 相关副作用。ZSJ-0228凭借其出色的疗效和卓越的安全性，有望成为LN长期临床管理的新疗法。