Key Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091, P. R. China.
Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, 650091, P. R. China.
Colloids Surf B Biointerfaces. 2023 Oct;230:113489. doi: 10.1016/j.colsurfb.2023.113489. Epub 2023 Aug 1.
Drug-induced liver injury (DILI) is a commonly encountered and diagnostically complex etiology of acute liver failure, characterized by early indications of hepatic oxidative stress. The most economical approach for DILI treatment is effective and durable oxidative stress prevention. Herein, we propose a long-lasting nanoantioxidant called PDA-Zn-BAI NPs characterized by sustained-release of baicalein (a natural antioxidant) for the long-lasting prevention of DILI. It is constructed using dopamine as an intermediate and layer-by-layer reinforcement strategy based on Zn-mediated coordination bonding, π-π stacking, and steric hindrance made of polydopamine network. Optimized PDA-Zn-BAI NPs performed a satisfactory sustained-release effect (36.67% ± 6.67 in normal condition and 60.32% ± 3.19 in acid condition of cumulative release within 5 days). Furthermore, it's been found that PDA-Zn-BAI NPs could continuously be accumulated in the liver with negligible hepatotoxicity and were activated to effectively scavenge reactive oxygen species to break off the damage of acetaminophen to the liver within 5 days (ALT as an indicator, > 70% prevention effect lasts for 5 days), which was vital for the long-lasting prevention of DILI. The long-lasting detoxification by PDA-Zn-BAI NPs in patients with DILI suggested a potential clinical application, especially for those patients who need prolonged administration of hepatotoxic drugs.
药物性肝损伤（DILI）是急性肝衰竭常见且诊断复杂的病因之一，其特征是早期存在肝氧化应激的迹象。DILI 治疗最经济的方法是有效且持久的氧化应激预防。在此，我们提出了一种名为 PDA-Zn-BAI NPs 的长效纳米抗氧化剂，其特点是持续释放黄芩素（一种天然抗氧化剂），以持久预防 DILI。它是使用多巴胺作为中间体，并通过基于 Zn 介导的配位键、π-π 堆积和由聚多巴胺网络构成的空间位阻的层层增强策略构建的。优化后的 PDA-Zn-BAI NPs 表现出令人满意的持续释放效果（在正常条件下为 36.67%±6.67%，在 5 天内累积释放的酸性条件下为 60.32%±3.19%）。此外，研究发现 PDA-Zn-BAI NPs 可以持续在肝脏中积累，具有可忽略的肝毒性，并在 5 天内被激活以有效清除活性氧，从而阻断对乙酰氨基酚对肝脏的损害（以 ALT 为指标，>70%的预防效果持续 5 天），这对于 DILI 的持久预防至关重要。PDA-Zn-BAI NPs 在 DILI 患者中的长效解毒作用表明其具有潜在的临床应用价值，特别是对于那些需要长期使用肝毒性药物的患者。
