背景:茶多酚(TP),绿茶的主要成分,具有显著的抗氧化和抗炎特性。然而,它们的治疗潜力是有限的,由于低吸收和低生物利用度。为了解决这一限制并提高其功效,我们通过将血小板膜(PM)包被在聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒(NPs)上,开发了一种仿生纳米平台,从而为TPs(PM@TP/NPs)提供靶向给哮喘炎症组织的载体.
方法:合成并表征PM@TP/NP后,我们通过细胞活力试验评估了它们的生物相容性和生物安全性,溶血试验,体内和体外炎症分析。然后使用HDM诱导的哮喘的小鼠模型评价PM@TP/NP对哮喘的治疗作用。此外,PM@TP/NPs介导的活性氧(ROS)清除能力,以及信号通路的激活,通过流式细胞术在HBE细胞和哮喘小鼠中进行分析,RT-qPCR,和西方印迹。
结果:与免费TP相比,PM@TP/NP在体外和体内均表现出优异的生物相容性和安全性,以及增强在发炎的肺中的保留。在HDM诱导的小鼠哮喘模型中,与游离TP相比,吸入PM@TP/NP大大减轻了肺部炎症,并减少了肺部2型促炎细胞因子的分泌。PM@TP/NP对哮喘的治疗作用可能与增强的ROS清除能力有关,Nrf2/HO-1通路的激活增加,并降低了肺中CCL2/MAPK和TLR4/NF-κB通路的激活。
结论:我们的发现表明,吸入PM@TP/NPs在很大程度上减轻了HDM诱导的哮喘小鼠的肺部炎症。这些结果表明PM@TP/NP可能是哮喘的一种新的治疗策略。
BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma.
METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting.
RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs.
CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.