Supramolecular self-assembled nanoparticles mediate oral delivery of therapeutic TNF-α siRNA against systemic inflammation.
Supramolecular self-assembled nanoparticles mediate oral delivery of therapeutic TNF-α siRNA against systemic inflammation.
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DOI：
10.1002/anie.201209991
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发表时间：
2013-05-27
影响因子：
16.6
通讯作者：
Cheng, Jianjun
中科院分区：
文献类型：
--
作者：
Yin, Lichen;Song, Ziyuan;Qu, Qiuhao;Kim, Kyung Hoon;Zheng, Nan;Yao, Catherine;Chaudhury, Isthier;Tang, Haoyu;Gabrielson, Nathan P.;Uckun, Fatih M.;Cheng, Jianjun
用肿瘤坏死因子-α单抗或受体干预炎症级联反应是临床免疫治疗炎症性疾病的主要方法，但存在成本高、自身免疫性差、副作用多等问题。[2-13]它的高效和特异性使其成为一种有前途的治疗肿瘤坏死因子-α介导的炎性疾病的范例。[14-18]最近有报道称，通过将map4k4siRNA口服递送到肠道相关巨噬细胞(GAM)来减轻全身炎症，证明了siRNA的治疗潜力。[19]由于GAM渗透到系统网状内皮组织，Map4k4siRNA介导的肿瘤坏死因子-α在GAM中的敲除延伸到其他组织，从而诱导全身抗炎作用。[19]尽管它具有生物学效力，但由于缺乏有效的递送技术，口服递送siRNA的临床潜力一直受到阻碍。SiRNA是阴离子的，亲水性的，很容易被体内的核酸酶降解。因此，它不能在恶劣的胃肠道条件下存活，也不能有效地穿透目标细胞的肠道上皮或细胞膜。因此，不仅需要有效的载体来保护siRNA在胃肠道中的降解，还需要有效的载体来促进肠道吸收和巨噬细胞的转染，从而最大化口服siRNA在体内的RNAi效率和抗炎作用。
Intervention of the inflammation cascade with tumor necrosis factor-α (TNF-α) monoclonal antibodies or receptors represents a major approach in clinical immunotherapy against inflammatory diseases, which however, often suffers from high cost, autoimmunity to antibodies, and various side effects.[1] siRNA-mediated RNA interference (RNAi) has recently emerged as a potent modality in regulating gene expression by suppressing mRNA translation;[2-13] its high efficiency and specificity has made it a promising treatment paradigm for TNF-α-mediated inflammatory disorders.[14-18] The therapeutic potential of siRNA was recently exemplified by a report of attenuating systemic inflammation by targeting orally delivered Map4k4 siRNA to gut-associated macrophages (GAMs).[19] Owing to the infiltration of GAMs to systemic reticuloendothelial tissues, Map4k4 siRNA-mediated TNF-α knockdown in GAMs extended to other tissues and thus induced systemic anti-inflammatory effects.[19]Despite its biological potency, the clinical potential of orally delivered siRNA has been hampered by the lack of efficient delivery technologies. siRNA is anionic, hydrophilic, and easily degraded by nucleases in the body. As such, it cannot survive the harsh condition of the gastrointestinal (GI) tract or effectively penetrate the intestinal epithelia or membranes of target cells.[20, 21] Hence, an effective carrier is needed not only to protect siRNA from degradation in the GI tract but also to improve the intestinal absorption as well as transfection in macrophages,[22] thereby maximizing the in vivo RNAi efficiency and antiinflammatory effect of orally delivered siRNA.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
14
作者：
Laroui, Hamed;Theiss, Arianne L.;Yan, Yutao;Dalmasso, Guillaume;Nguyen, Hang T. T.;Sitaraman, Shanthi V.;Merlin, Didier
通讯作者：
Merlin, Didier
影响因子：
16.6
作者：
Gabrielson, Nathan P.;Lu, Hua;Yin, Lichen;Li, Dong;Wang, Fei;Cheng, Jianjun
通讯作者：
Cheng, Jianjun
影响因子：
46.9
作者：
Dassie, Justin P.;Liu, Xiu-ying;Thomas, Gregory S.;Whitaker, Ryan M.;Thiel, Kristina W.;Stockdale, Katie R.;Meyerholz, David K.;McCaffrey, Anton P.;McNamara, James O., II;Giangrande, Paloma H.
通讯作者：
Giangrande, Paloma H.
影响因子：
16.6
作者：
Jayaraman, Muthusamy;Ansell, Steven M.;Mui, Barbara L.;Tam, Ying K.;Chen, Jianxin;Du, Xinyao;Butler, David;Eltepu, Laxman;Matsuda, Shigeo;Narayanannair, Jayaprakash K.;Rajeev, Kallanthottathil G.;Hafez, Ismail M.;Akinc, Akin;Maier, Martin A.;Tracy, Mark A.;Cullis, Pieter R.;Madden, Thomas D.;Manoharan, Muthiah;Hope, Michael J.
通讯作者：
Hope, Michael J.