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Nanoengineered immunosuppressive therapeutics modulating M1/M2 macrophages into the balanced status for enhanced idiopathic pulmonary fibrosis therapy.
Nanoscale ( IF 6.7 ) Pub Date : 2020-04-30 , DOI: 10.1039/d0nr00750a
Xin Chang 1 , Lei Xing , Yi Wang , Tian-Jiao Zhou , Li-Jun Shen , Hu-Lin Jiang
Affiliation  

Effective treatment in clinic for idiopathic pulmonary fibrosis (IPF) remains a challenge due to low drug accumulation in lungs and imbalanced polarization of pro/anti-inflammatory macrophages (M1/M2 macrophages). Herein, a novel endogenous cell-targeting nanoplatform (PNCE) is developed for enhanced IPF treatment efficacy through modulating M1/M2 macrophages into the balanced status to suppress fibroblast over-activation. Notably, PNCE loaded with nintedanib (NIN) and colchicine (COL) can firstly target endogenous monocyte-derived multipotent cells (MOMCs) and then be effectively delivered into IPF lungs due to the homing ability of MOMCs, and detached sensitively from MOMCs by matrix metalloproteinases-2 (MMP-2) over-expressed in IPF lungs. After PNCE selectively accumulated within fibrosis foci, COL can mildly modulate the polarization of M1 macrophages into M2 macrophages to balance innate immune responses, which can enhance the suppressing effect of NIN on fibroblast activation, further improving the IPF therapy. Altogether, PNCE has two collaborative steps including the inhibition of innate immune responses accompanied by the decrease of fibroblast populations in IPF lungs, achieving a stronger and excellent anti-fibrotic efficacy both in vitro and in vivo. This endogenous cell-based engineered liposomal nanoplatform not only allows therapeutic drugs to take effect selectively in vivo, but also provides an alternative strategy for an enhanced curative effect by modulating innate immune responses in IPF therapy.

中文翻译:

纳米工程免疫抑制疗法可将M1 / M2巨噬细胞调节至平衡状态,以增强特发性肺纤维化治疗。

由于肺部药物堆积少和促炎/抗炎巨噬细胞(M1 / M2巨噬细胞)极化不平衡,临床上有效治疗特发性肺纤维化(IPF)仍然是一个挑战。本文中,开发了一种新型的内源性靶向细胞纳米平台(PNCE),用于通过将M1 / M2巨噬细胞调节至平衡状态来抑制成纤维细胞过度活化,从而提高IPF的治疗效果。值得注意的是,负载有任他尼丹(NIN)和秋水仙碱(COL)的PNCE可以首先靶向内源性单核细胞衍生的多能细胞(MOMC),然后由于MOMC的归巢能力而被有效地递送到IPF肺中,然后通过基质金属蛋白酶与MOMC灵敏地分离。 -2(MMP-2)在IPF肺中过度表达。PNCE在纤维化病灶内选择性积聚后,COL可以温和地将M1巨噬细胞的极化调节为M2巨噬细胞,以平衡先天免疫反应,从而可以增强NIN对成纤维细胞活化的抑制作用,从而进一步改善IPF治疗。总体而言,PNCE具有两个协作步骤,包括抑制先天免疫应答并伴随IPF肺中成纤维细胞数量的减少,从而在体外和体内均获得更强,更优异的抗纤维化功效。这种基于细胞的内源性工程脂质体纳米平台不仅允许治疗药物在体内选择性地发挥作用,而且还提供了通过调节IPF治疗中的先天免疫应答来增强疗效的替代策略。可以增强NIN对成纤维细胞活化的抑制作用,从而进一步改善IPF治疗。总体而言,PNCE具有两个协作步骤,包括抑制先天免疫应答并伴随IPF肺中成纤维细胞数量的减少,从而在体外和体内均获得更强,更优异的抗纤维化功效。这种基于细胞的内源性工程脂质体纳米平台不仅允许治疗药物在体内选择性地发挥作用,而且还提供了通过调节IPF治疗中的先天免疫应答来增强疗效的替代策略。可以增强NIN对成纤维细胞活化的抑制作用,从而进一步改善IPF治疗。总体而言,PNCE具有两个协作步骤,包括抑制先天免疫应答并伴随IPF肺中成纤维细胞数量的减少,从而在体外和体内均获得更强,更优异的抗纤维化功效。这种基于细胞的内源性工程脂质体纳米平台不仅允许治疗药物在体内选择性地发挥作用,而且还提供了通过调节IPF治疗中的先天免疫应答来增强疗效的替代策略。在体内和体外均具有更强,更优异的抗纤维化功效。这种基于细胞的内源性工程脂质体纳米平台不仅允许治疗药物在体内选择性地发挥作用,而且还提供了通过调节IPF治疗中的先天免疫应答来增强疗效的替代策略。在体内和体外均具有更强,更优异的抗纤维化功效。这种基于细胞的内源性工程脂质体纳米平台不仅允许治疗药物在体内选择性地发挥作用,而且还提供了通过调节IPF治疗中的先天免疫应答来增强疗效的替代策略。
更新日期:2020-03-30
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