Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430030, China.
ACS Nano. 2022 Sep 27;16(9):15124-15140. doi: 10.1021/acsnano.2c06357. Epub 2022 Aug 29.
Acute respiratory distress syndrome (ARDS) has been a life threat for patients in ICUs. Vast efforts have been devoted, while no medication has proved viable, which may be ascribed to inadequate drug delivery to damaged tissues and insufficient control of lung inflammation. Given the anti-inflammatory role of M2-type macrophages, M2 macrophage-derived nanovesicles and lung-targeting liposomes are cofused to fabricate hybrid liposomes-nanovesicles (LNVs). Benefiting from the incorporated lung-homing moiety, LNVs demonstrate high pulmonary accumulation with a lung/liver ratio of 14.9, which is approximately 53.3-fold of free nanovesicles. Thus, M2 macrophage-derived nanovesicles can be delivered to lung tissues for executing immunoregulatory functions. LNVs display phagocytosis by the infiltrated neutrophils and macrophages, exhibiting sustained release of preloaded IKK-2 inhibitor (TPCA-1). The integrated nanosystems demonstrate multidimensional suppression of the overwhelming inflammation, such as decreasing infiltration of inflammatory cells, achieving restraint on cytokine storms and alleviating oxidative stress. Therefore, the improved therapeutic outcome in ARDS mice is obtained. Altogether, the hybrid nanoplatform provides a versatile drug delivery paradigm for integrating biological nanovesicles and therapeutic molecules by cofusion of nanovesicles with liposomes, improving lung biodistribution and accomplishing a boosted anti-inflammatory response for ARDS therapy.
急性呼吸窘迫综合征（ARDS）一直是 ICU 患者的生命威胁。尽管已经做出了巨大的努力，但没有一种药物被证明是可行的，这可能是由于药物输送到受损组织的不足和对肺部炎症的控制不足。鉴于 M2 型巨噬细胞的抗炎作用，M2 巨噬细胞衍生的纳米囊泡和肺靶向脂质体被融合来制备混合脂质体-纳米囊泡（LNVs）。由于整合了肺部归巢部分，LNVs 表现出高肺部积累，肺/肝比为 14.9，是游离纳米囊泡的约 53.3 倍。因此，M2 巨噬细胞衍生的纳米囊泡可以递送到肺部组织，以执行免疫调节功能。LNVs 被浸润的中性粒细胞和巨噬细胞吞噬，表现出预先加载的 IKK-2 抑制剂（TPCA-1）的持续释放。整合的纳米系统表现出对过度炎症的多维抑制，例如减少炎症细胞的浸润，抑制细胞因子风暴，减轻氧化应激。因此，在 ARDS 小鼠中获得了改善的治疗效果。总之，该杂交纳米平台通过将纳米囊泡与脂质体融合，为整合生物纳米囊泡和治疗分子提供了一种通用的药物输送范例，提高了肺部的生物分布，并实现了增强的抗炎反应，用于 ARDS 治疗。
