A New Formyl Peptide Receptor-1 Antagonist Conjugated Fullerene Nanoparticle for Targeted Treatment of Degenerative Disc Diseases.
A New Formyl Peptide Receptor-1 Antagonist Conjugated Fullerene Nanoparticle for Targeted Treatment of Degenerative Disc Diseases.
复制标题
DOI：
10.1021/acsami.9b11783
复制
发表时间：
2019-09
影响因子：
9.5
通讯作者：
Li Xiao;Rong Huang;Yi Zhang;Tinghui Li;Jun Dai;Naga Nannapuneni;Timothy R. Chastanet;Matthew Chen;F. Shen;Li Jin;H. Dorn;X. Li
中科院分区：
文献类型：
--
作者：
Li Xiao;Rong Huang;Yi Zhang;Tinghui Li;Jun Dai;Naga Nannapuneni;Timothy R. Chastanet;Matthew Chen;F. Shen;Li Jin;H. Dorn;X. Li
腰椎间盘退变伴背痛是世界范围内最常见的致残原因，然而，目前还没有安全有效的治疗方法。在这里，我们报道了一种新的功能化纳米富勒烯，它与一种能与活化的巨噬细胞上表达的甲酰肽受体-1(FPR-1)特异性结合的多肽相结合。通过荧光染料将羧基C60与多肽的伯胺基团偶联，合成了一种新的纳米粒子(又名FT-C60)。用X射线光电子能谱、质谱学和凝胶电泳法对新纳米粒子进行了表征。在电子顺磁共振波谱中，它具有有效清除自由基(羟基和超氧阴离子)的能力。在培养细胞中，纳米FT-C60优先与活化的巨噬细胞上的FPR-1结合，并显著降低包括IL-6、IL-1、肿瘤坏死因子-α和环氧合酶-2在内的促炎因子的mRNA表达。体内动物实验表明，一次静脉注射FT-C60可有效缓解已建立的小鼠神经根病模型术后12天的疼痛。小鼠脊柱的体外近红外荧光成像证实了FT-C60在术后第14天具有靶向性。脊柱切片的组织学染色定量分析表明，与仅在术后第7天的损伤相比，纳米FT-C60显著减轻了损伤局部的炎症。综上所述，我们开发了一种新型的靶向纳米颗粒，通过全身给药治疗腰椎神经根病。这是开发一种新的靶向和系统的纳米颗粒疗法来治疗退行性腰椎间盘疾病的首个同类研究。
Intervertebral disc degeneration associated back pain is the most common cause of disability worldwide, however, no safe and effective treatment have been available. Here, we report a new functionalized nanofullerene conjugated with a peptide that binds specifically to a formyl peptide receptor - 1 (FPR-1) expressed on activated macrophages. The new nanoparticle (aka FT-C60) was synthesized by conjugating carboxyl-C60 with the primary amine group of the peptide with a fluorescence dye for easy detection. The new nanoparticle was characterized by X-ray photoelectron spectroscopy, mass spectroscopy, and gel electrophoresis. It possessed effective radical (hydroxyl and superoxide anions) scavenging capabilities in electron paramagnetic resonance spectroscopy. In cultured cells, the nanoparticle FT-C60 demonstrated preferential binding to FPR-1 on activated macrophages and significantly attenuated mRNA expression of pro-inflammatory factors including interleukin-6, interleukin-1, tumor necrosis factor-alpha, and cyclooxygenase-2. In vivo animal study exhibited that a single intravenous injection of FT-C60 effectively alleviated pain in an established mouse model of radiculopathy for up to post-operation day (POD) 12. Ex vivo near-infrared fluorescence imaging of mouse spine confirmed the targeting property of FT-C60 towards the injured disc on POD 14. Quantitative analysis of histological staining on spine sections showed that nanoparticle FT-C60 dramatically reduced inflammation at local injury site compared to injury only on POD 7. In summary, we developed a novel targeted nanoparticle for treatment of lumbar radiculopathy by systemic delivery. This is a first-of-its-kind study for developing a novel class of targeted and systemic nanoparticle therapeutics to treat degenerative disc diseases.