A photothermal-triggered nitric oxide nanogenerator combined with siRNA for precise therapy of osteoarthritis by suppressing macrophage inftammation
A photothermal-triggered nitric oxide nanogenerator combined with siRNA for precise therapy of osteoarthritis by suppressing macrophage inftammation
复制标题
光热触发一氧化氮纳米发生器结合siRNA通过抑制巨噬细胞炎症精确治疗骨关节炎
DOI：
10.1039/c8nr10013f
复制
发表时间：
2019-04-14
期刊：
影响因子：
6.7
通讯作者：
Ye, Gang
中科院分区：
文献类型：
--
作者：
Chen, Xu;Liu, Yanan;Ye, Gang
虽然一氧化氮（NO）可以通过抑制炎症来治疗骨关节炎（OA），但在炎症细胞中精确控制NO释放的方法仍然难以捉摸。本文通过在纳米颗粒内组装光热剂和NO分子，构建了光热触发NO纳米发生器NO-Hb@siRNMaPLGA-PEG （NHsPP）。在NHsPP纳米颗粒中，血红蛋白（Hb）纳米颗粒可以作为NO载体，吸收650 nm （0.5 W cm(-2)）的近红外光并将其转化为热量，从而触发NO的释放。此外，在装载Notchl-siRNA后，可以实现精确处理。此外，利用光热疗法的协同效应，NHsPP纳米颗粒实现了NO、siRNA和PTT的同时处理。通过这种联合治疗，与仅使用NO、siRNA或PTT的治疗组相比，NHsPP纳米颗粒的治疗效果显著增强。这种联合疗法通过降低促炎细胞因子水平和巨噬细胞反应有效抑制炎症反应。随后，在双峰成像引导下，NHsPP纳米颗粒不仅能在OA小鼠体内有效蓄积，还能减少炎症反应，有效防止软骨糜坏，且对主要器官无毒副作用。因此，这种新型的基于光热纳米颗粒的no释放系统有望成为临床炎症性疾病治疗的潜在替代方案，当与其他纳米治疗系统结合时，可能提供图像指导。
Although nitric oxide (NO) can be used to treat osteoarthritis (OA) by inhibiting inflammation, a method for the accurately controlled release of NO in inflammatory cells is still elusive. Herein, photothermal-trig-gered NO nanogenerators NO-Hb@siRNMaPLGA-PEG (NHsPP) were constructed by assembling photo-thermal-agents and NO molecules within nanoparticles. In the NHsPP nanoparticles the hemoglobin (Hb) nanoparticles can act as a NO carrier which can absorb near-infrared light at 650 nm (0.5 W cm(-2)) and convert it into heat to trigger the release of NO. Moreover, after loading Notchl-siRNA, precise treatment can be achieved. Furthermore, using the synergistic effect of photothermal therapy, the NHsPP nano-particles achieved simultaneous treatment with NO, siRNA and PTT. Through this combination therapy, the therapeutic effect of the NHsPP nanoparticles was significantly enhanced compared to the treatment groups using only NO, siRNA or PTT. This combination therapy inhibits the inflammatory response effectively by reducing the level of pro-inflammatory cytokines and the macrophage response. Subsequently, guided by dual-modal imaging, the NHsPP nanoparticles can not only accumulate effectively in OA mice, but can also reduce the inflammatory response and efficiently prevent cartilage erosion, without causing toxic side effects in the major organs. Therefore, this novel photothermal nanoparticle-based NO-releasing system is expected to be a potential alternative for clinical inflammatory disease therapy and may provide image guidance when combined with other nanotherapy systems.