Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, China.
School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China.
Biomater Sci. 2023 Sep 12;11(18):6223-6235. doi: 10.1039/d3bm00802a.
Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles were extracted and coated onto the surface of the NPs to constitute the biomimetic PM@TP-NPs. In a LPS-induced ALI mouse model, PM@TP-NPs showed good biocompatibility and biosafety, which was evidenced by no significant toxic effect on cell viability and no hemolysis of red blood cells. In ALI mice, the PM@TP-NPs showed favorable anti-inflammation and enhanced therapeutic activity of TPs compared to the free drug. Administration of PM@TP-NPs effectively inhibited lung vascular injury, evidenced by the decreased lung vascular permeability, reduced pro-inflammatory cytokine burden, evidenced by decreased inflammatory cell (macrophages, neutrophils, .) infiltration in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited the secretion of pro-inflammatory cytokines and NLRP3 inflammasome activation. ALI/ARDS is defined by damage to the alveolar epithelium and endothelium; thus, effective intervention targeting pulmonary vascular endothelial cells (VECs) is crucial for the treatment of respiratory diseases. For further determination of the targeting of PM cloaked NPs, healthy mice were also administered with the same NPs. Interestingly, the PM cloaked NPs only showed highly efficient targeting to the inflamed lungs and VECs, but no accumulation in healthy lungs and VECs. The data demonstrated that this biomimetic nanoplatform could be used as a potential strategy for personalized therapies in the treatment of inflammatory diseases, such as ALI/ARDS, and even COVID-19-associated pneumonia.
ALI（急性肺损伤）/ARDS（急性呼吸窘迫综合征）患者通常伴有脓毒症和预后不良，导致死亡率高达 25-40%。尽管医学取得了进步，但由于全身循环时间短和肺部特异性差，ALI/ARDS 仍然没有有效的药物治疗方法。为了解决这个问题，我们通过乳化蒸发法制备了负载 TP 的纳米颗粒（TP-NPs），然后提取血小板膜囊泡并涂覆在 NPs 表面，构成仿生 PM@TP-NPs。在 LPS 诱导的 ALI 小鼠模型中，PM@TP-NPs 表现出良好的生物相容性和生物安全性，这表现在对细胞活力没有显著的毒性作用，也没有红细胞溶血。在 ALI 小鼠中，与游离药物相比，PM@TP-NPs 表现出更好的抗炎作用和增强 TP 的治疗活性。PM@TP-NPs 的给药有效地抑制了肺血管损伤，表现为肺血管通透性降低，促炎细胞因子负担减轻，支气管肺泡灌洗液（BALF）和肺组织中炎症细胞（巨噬细胞、中性粒细胞等）浸润减少，以及促炎细胞因子的分泌和 NLRP3 炎性小体的激活受到抑制。ALI/ARDS 的定义是肺泡上皮和内皮细胞受损；因此，针对肺血管内皮细胞（VECs）的有效干预对于治疗呼吸系统疾病至关重要。为了进一步确定 PM 包裹纳米颗粒的靶向性，我们还在健康小鼠中给予了相同的 NPs。有趣的是，PM 包裹的纳米颗粒仅显示出对发炎肺部和 VECs 的高效靶向性，而在健康肺部和 VECs 中没有积累。这些数据表明，这种仿生纳米平台可作为治疗炎症性疾病（如 ALI/ARDS，甚至 COVID-19 相关肺炎）的个性化治疗的潜在策略。
