Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment.
Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment.
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巨噬细胞靶向肺给药地塞米松通过调节免疫微环境改善肺纤维化治疗。
DOI：
10.3389/fimmu.2021.613907
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Sang X;Wang Y;Xue Z;Qi D;Fan G;Tian F;Zhu Y;Yang J
特发性肺纤维化（IPF）是一种严重的慢性肺部疾病，治疗方法有限。炎症和免疫障碍被认为是肺纤维化发生和发展的主要因素。受巨噬细胞在炎症和免疫疾病过程中的关键作用的启发，在这里，我们报告了一种新的方法，用于在体外和体内将药物直接递送到原位纤维化组织部位。首先，制备含有地塞米松（Dex-L）的脂质体并设计成在早期进入巨噬细胞，形成巨噬细胞负载的Dex-L递送系统（Dex-L-MV）。测定趋化因子和细胞因子因子如IL-6、IL-10、Arg-1以显示Dex-L对各种亚型巨噬细胞的作用。接下来，我们通过共培养极化/失活的巨噬细胞和成纤维细胞来模拟炎症和抗炎微环境，以显示Dex-L-MV的急性炎症反应。此外，我们证实了Dex-L-MV在体内向炎症部位的靶向递送，并且令人惊讶地发现，注射的含有Dex的巨噬细胞可以降低纤维化阶段期间巨噬细胞浸润的水平和胶原沉积标志物的表达，同时几乎不引起全身毒性。这些数据证明了Dex-L-MV对于抗肺过程的适用性和免疫调节作用。据设想，这些发现是朝着内源性免疫靶向系统作为临床药物递送工具迈出的一步。
Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of inflammation and immune disorders, here, we report a new method for direct drug delivery into the in-situ fibrotic tissue sites in vitro and in vivo. First, liposomes containing dexamethasone (Dex-L) are prepared and designed to entry into the macrophages in the early hours, forming the macrophages loaded Dex-L delivery system (Dex-L-MV). Chemokine and cytokine factors such as IL-6, IL-10, Arg-1 are measured to show the effect of Dex-L to the various subtypes of macrophages. Next, we mimic the inflammatory and anti-inflammatory microenvironment by co-culture of polarized/inactive macrophage and fibroblast cells to show the acute inflammation response of Dex-L-MV. Further, we confirm the targeted delivery of Dex-L-MV into the inflammatory sites in vivo, and surprisingly found that injected macrophage containing Dex can reduce the level of macrophage infiltration and expression of the markers of collagen deposition during the fibrotic stage, while causing little systematic toxicity. These data demonstrated the suitability and immune regulation effect of Dex-L-MV for the anti-pulmonary process. It is envisaged that these findings are a step forward toward endogenous immune targeting systems as a tool for clinical drug delivery.
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DOI：
10.1084/jem.20162152
发表时间：
2017-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Misharin AV;Morales-Nebreda L;Reyfman PA;Cuda CM;Walter JM;McQuattie-Pimentel AC;Chen CI;Anekalla KR;Joshi N;Williams KJN;Abdala-Valencia H;Yacoub TJ;Chi M;Chiu S;Gonzalez-Gonzalez FJ;Gates K;Lam AP;Nicholson TT;Homan PJ;Soberanes S;Dominguez S;Morgan VK;Saber R;Shaffer A;Hinchcliff M;Marshall SA;Bharat A;Berdnikovs S;Bhorade SM;Bartom ET;Morimoto RI;Balch WE;Sznajder JI;Chandel NS;Mutlu GM;Jain M;Gottardi CJ;Singer BD;Ridge KM;Bagheri N;Shilatifard A;Budinger GRS;Perlman H
通讯作者：
Perlman H
巨噬细胞膜伪装金纳米壳可延长体内循环寿命并增强癌症光热治疗
影响因子：
9.5
作者：
Xuan, Mingjun;Shao, Jingxin;He, Qiang
通讯作者：
He, Qiang
影响因子：
10.6
作者：
Chanda D;Otoupalova E;Smith SR;Volckaert T;De Langhe SP;Thannickal VJ
通讯作者：
Thannickal VJ
影响因子：
10.8
作者：
Ayer, Maxime;Klok, Harm-Anton
通讯作者：
Klok, Harm-Anton
影响因子：
12.4
作者：
Tang, Tao-Tao;Lv, Lin-Li;Liu, Bi-Cheng
通讯作者：
Liu, Bi-Cheng