Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis.
Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis.
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DOI：
10.1021/acsnano.6b01114
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发表时间：
2016-05-24
期刊：
影响因子：
17.1
通讯作者：
Farokhzad, Omid C.
中科院分区：
文献类型：
--
作者：
Kamaly, Nazila;Fredman, Gabrielle;Fojas, Jhalique Jane R.;Subramanian, Manikandan;Choi, Won Ii;Zepeda, Katherine;Vilos, Cristian;Yu, Mikyung;Gadde, Suresh;Wu, Jun;Milton, Jaclyn;Leitao, Renata Carvalho;Fernandes, Livia Rosa;Hasan, Moaraj;Gao, Huayi;Vance Nguyen;Harris, Jordan;Tabas, Ira;Farokhzad, Omid C.
炎症是一种基本的保护性生物反应，涉及细胞因子和免疫信号分子之间的协调级联信号，其促进急性损伤或感染后组织稳态的恢复。然而，在动脉粥样硬化等慢性炎症性疾病中，炎症并不能有效解决，并可能导致组织损伤和基础疾病的恶化。抑制炎症和增强消退的治疗剂目前受到相当大的关注，特别是那些以最小的宿主附带损害缓和炎症的治疗剂。在这里，我们提出了控制释放的聚合物纳米粒子纳入抗炎细胞因子白细胞介素10（IL-10）靶向输送到动脉粥样硬化斑块的发展和疗效调查。通过使用能够产生暴露于有机溶剂后具有保留的IL-10生物活性的纳米颗粒的快速微混合器芯片进行纳米沉淀，经由生物可降解聚酯聚合物的自组装来纳米工程化纳米颗粒。采用系统的组合方法筛选纳米颗粒，从体外和离体研究中获得最佳生物活性制剂。称为Col-IV IL-10 NP 22的最有效的纳米颗粒显著缓和自限性腹膜炎模型中的急性炎症，并且显示出比天然IL-10更有效。此外，Col-IV IL-10纳米颗粒通过增加纤维帽厚度和减少高脂喂养的LDLr−/−小鼠晚期病变中的坏死核心来防止易损斑块形成。这些结果证明了这种工程化纳米颗粒用于控制递送有效的IL-10细胞因子以治疗动脉粥样硬化的功效和促消退潜力。
Inflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage. Here we present the development and efficacy investigations of controlled-release polymeric nanoparticles incorporating the anti-inflammatory cytokine interleukin 10 (IL-10) for targeted delivery to atherosclerotic plaques. Nanoparticles were nanoengineered via self-assembly of biodegradable polyester polymers by nanoprecipitation using a rapid micromixer chip capable of producing nanoparticles with retained IL-10 bioactivity post-exposure to organic solvent. A systematic combinatorial approach was taken to screen nanoparticles, resulting in an optimal bioactive formulation from in vitro and ex vivo studies. The most potent nanoparticle termed Col-IV IL-10 NP22 significantly tempered acute inflammation in a self-limited peritonitis model and was shown to be more potent than native IL-10. Furthermore, the Col-IV IL-10 nanoparticles prevented vulnerable plaque formation by increasing fibrous cap thickness and decreasing necrotic cores in advanced lesions of high fat-fed LDLr−/− mice. These results demonstrate the efficacy and pro-resolving potential of this engineered nanoparticle for controlled delivery of the potent IL-10 cytokine for the treatment of atherosclerosis.
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影响因子：
20.3
作者：
Gautier, Emmanuel L.;Ivanov, Stoyan;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
4.4
作者：
Lauw, FN;Pajkrt, D;van der Poll, T
通讯作者：
van der Poll, T
影响因子：
32.4
作者：
Buckley, Christopher D.;Gilroy, Derek W.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
1.3
作者：
Iyer SS;Cheng G
通讯作者：
Cheng G
DOI：
10.1111/j.1742-4658.2012.08739.x
发表时间：
2012-10
期刊：
The FEBS journal
影响因子：
--
作者：
Capiralla H;Vingtdeux V;Venkatesh J;Dreses-Werringloer U;Zhao H;Davies P;Marambaud P
通讯作者：
Marambaud P