Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DNA for the treatment of experimental arthritis.
Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DNA for the treatment of experimental arthritis.
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DOI：
10.1016/j.biomaterials.2015.05.028
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发表时间：
2015-08
期刊：
影响因子：
14
通讯作者：
Amiji, Mansoor
中科院分区：
文献类型：
--
作者：
Jain, Shardool;Thanh-Huyen Tran;Amiji, Mansoor
关键词：
在这项研究中，我们首次证明了非病毒基因转染策略将巨噬细胞从M1功能亚型重新激活为M2功能亚型用于治疗类风湿性关节炎（RA）的有效性。将编码抗炎（IL-10）细胞因子的质粒DNA成功地包封到基于非凝聚藻酸盐的纳米颗粒中，并且用tuftsin肽修饰纳米载体的表面以实现主动的巨噬细胞靶向。在腹膜内给药后，在关节炎大鼠的发炎爪中观察到簇蛋白酶修饰的藻酸盐纳米颗粒的增强的定位。重要的是，靶向纳米颗粒治疗在重编程巨噬细胞表型平衡中是成功的，因为来自用IL-10质粒DNA负载的tuftsin/藻酸盐纳米颗粒治疗的关节炎大鼠的约66%的总滑膜巨噬细胞处于M2状态，相比之下，来自未治疗的关节炎大鼠的约9%的巨噬细胞处于M2状态。治疗显著降低了全身和关节组织促炎细胞因子（TNF-α、IL-1β和IL-6）的表达，并阻止了炎症和关节损伤的进展，如磁共振成像和组织学所示。治疗使动物能够在整个研究过程中保持其活动性，而未治疗的动物的活动性受损。总的来说，这项研究表明，载有IL-10质粒DNA的靶向藻酸盐纳米颗粒可以有效地将巨噬细胞从M1状态恢复到M2状态，为治疗慢性炎症性疾病提供了一种新的治疗模式。
In this study, we have shown for the first time the effectiveness of a non-viral gene transfection strategy to re-polarize macrophages from M1 to M2 functional sub-type for the treatment of rheumatoid arthritis (RA). An anti-inflammatory (IL-10) cytokine encoding plasmid DNA was successfully encapsulated into non-condensing alginate based nanoparticles and the surface of the nano-carriers was modified with tuftsin peptide to achieve active macrophage targeting. Enhanced localization of tuftsin-modified alginate nanoparticles was observed in the inflamed paws of arthritic rats upon intraperitoneal administration. Importantly, targeted nanoparticle treatment was successful in reprogramming macrophage phenotype balance as ~66% of total synovial macrophages from arthritic rats treated with the IL-10 plasmid DNA loaded tuftsin/alginate nanoparticles were in the M2 state compared to ~9% of macrophages in the M2 state from untreated arthritic rats. Treatment significantly reduced systemic and joint tissue pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression and prevented the progression of inflammation and joint damage as revealed by magnetic resonance imaging and histology. Treatment enabled animals to retain their mobility throughout the course of study, whereas untreated animals suffered from impaired mobility. Overall, this study demonstrates that targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state, offering a novel treatment paradigm for treatment of chronic inflammatory diseases.
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影响因子：
5
作者：
Li, Jun;Hsu, Hui-Chen;Mountz, John D.
通讯作者：
Mountz, John D.
影响因子：
3.6
作者：
Cai, X.;Wong, Y. F.;Liu, L.
通讯作者：
Liu, L.
影响因子：
5.6
作者：
BARSHAVIT, Z;GOLDMAN, R;FRIDKIN, M
通讯作者：
FRIDKIN, M
影响因子：
6.7
作者：
Edwards, CJ
通讯作者：
Edwards, CJ
DOI：
10.1161/atvbaha.112.300068
发表时间：
2013-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Liu G;Abraham E
通讯作者：
Abraham E