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磁性脂质体作为一种用于特发性肺纤维化治疗的双靶向递送系统。

Magnetic liposome as a dual-targeting delivery system for idiopathic pulmonary fibrosis treatment.

作者信息

Wang Xi, Wang Yuying, Xue Zhifeng, Wan Weimin, Li Yixuan, Qin Honglin, Zhu Yan, Tian Fei, Yang Jian

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, China.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

出版信息

J Colloid Interface Sci. 2023 Apr 15;636:388-400. doi: 10.1016/j.jcis.2023.01.007. Epub 2023 Jan 6.

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, where M2 macrophages play an irreplaceable role in the anti-inflammatory progress. Targeting M2 macrophages and regulating their polarization may be a potential treatment strategy for IPF. Herein, we designed a magnetic liposome based dual-targeting delivery system for the IPF treatment, constructed by mannose-modified magnetic nanoparticles (MAN-MNPs) loaded on the surface of the liposome (MAN-MNPs@LP). The delivery system is capable of responding to a static magnetic field (SMF) and then recognizing in situ of M2 macrophages through the mannose receptor-dependent internalization. Firstly, a series of physical and chemical assays were used to characterize these nanoparticles. Subsequently, magnetic liposomes accumulation in the damaged lung with/without mannose modification and SMF were compared by in vivo imaging system. Finally, the reduction of M2 macrophages and inhibition of their polarization confirmed that the development of IPF was retarded due to the in situ release of encapsulated dexamethasone (Dex) in lungs under the SMF. Further investigation demonstrated that the expression of α-SMA and collagen deposition was reduced. Altogether, this dual-targeting delivery system can effectively deliver Dex into M2 macrophages in the lung, making it a novel and promising therapeutic system for the IPF treatment.

摘要

特发性肺纤维化(IPF)是特发性间质性肺炎最常见的形式,其中M2巨噬细胞在抗炎过程中发挥着不可替代的作用。靶向M2巨噬细胞并调节其极化可能是IPF的一种潜在治疗策略。在此,我们设计了一种基于磁性脂质体的双靶向递送系统用于IPF治疗,该系统由负载在脂质体表面的甘露糖修饰磁性纳米颗粒(MAN-MNPs)构建而成(MAN-MNPs@LP)。该递送系统能够响应静磁场(SMF),然后通过甘露糖受体依赖性内化作用原位识别M2巨噬细胞。首先,使用一系列物理和化学分析方法对这些纳米颗粒进行表征。随后,通过体内成像系统比较了有/无甘露糖修饰及SMF情况下磁性脂质体在受损肺中的蓄积情况。最后,M2巨噬细胞数量的减少及其极化的抑制证实,由于在SMF作用下肺中包裹的地塞米松(Dex)原位释放,IPF的发展受到了抑制。进一步研究表明,α-SMA的表达和胶原蛋白沉积减少。总之,这种双靶向递送系统能够有效地将Dex递送至肺中的M2巨噬细胞,使其成为一种用于IPF治疗的新型且有前景的治疗系统。

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