Abstract：
Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs.
摘要：
急性呼吸窘迫综合征（ARDS）是一种以严重肺部炎症为特征的危重病。提高递送效率和实现抗炎药在肺部炎症部位的控释是ARDS治疗中的主要挑战。利用肺血管通透性增加和微酸性炎症微环境，构建了基于地塞米松磷酸钠(DSP)和Ca2+的pH响应性矿化纳米粒子。通过M2巨噬细胞膜的进一步仿生修饰，混合矿化纳米囊泡（MM@LCaP）被设计为具有来自膜的免疫调节能力，并保持来自核心纳米颗粒的pH敏感性，以在酸性炎症条件下响应性药物释放。与健康小鼠相比，静脉注射后48小时，炎症小鼠中MM@LCaP的肺/肝积累增加了约5.5倍。MM@LCaP促进抗炎巨噬细胞的极化，镇静的炎症细胞因子，并表现出全面的治疗效果。此外，MM@LCaP改善了糖皮质激素的安全性。一起来看,基于混合矿化纳米囊泡的药物递送策略可能为提高临床药物的疗效和降低毒性提供有希望的思路。
