Amine Functionalized Trimetallic Nitride Endohedral Fullerenes: A Class of Nanoparticle to Tackle Low Back/Leg Pain.
Amine Functionalized Trimetallic Nitride Endohedral Fullerenes: A Class of Nanoparticle to Tackle Low Back/Leg Pain.
复制标题
DOI：
10.1021/acsabm.2c00269
复制
发表时间：
2022-06-20
影响因子：
4.7
通讯作者：
Li, Xudong
中科院分区：
文献类型：
--
作者：
Xiao, Li;Huang, Rong;Sulimai, Nurul;Yao, Ricky;Manley, Brock;Xu, Peng;Felder, Robin;Jin, Li;Dorn, Harry C;Li, Xudong
腰痛是最常见的健康问题，全世界的患病率超过80%，美国每年的成本估计为1000亿美元。腰椎间盘退变是下腰痛的主要原因。然而，仍然缺乏安全和有效的治疗来应对这种毁灭性的疾病。在本研究中，我们合成了四种功能化三金属氮化物金属富勒烯(羧基-f-Sc3N@C80、羧基-f-Gd3N@C80、氨基-f-Sc3N@C80和氨基-f-Gd3N@C80)，并用X-射线光电子能谱、基质辅助激光解吸电离飞行时间质谱仪和UV-Vis对它们进行了表征。通过电子顺磁共振，四种金属富勒烯衍生物都具有剂量依赖的自由基清除能力(羟基自由基和超氧阴离子)，其中最有希望的是胺官能化的C80金属富勒烯。在1μM时，氨基-f-Sc3N@C80和氨基-f-Gd3N@C80均可显著减少脂多糖诱导的巨噬细胞内活性氧的产生和促炎介质(iNOS、肿瘤坏死因子-α、IL-1和COX-2)的基因表达，但无明显的细胞毒性作用。此外，在已建立的腰神经根病小鼠模型中，氨基-f-Sc3N@C80和氨基-f-Gd3N@C80可有效减轻同侧机械性痛敏2周。在背根神经节组织块培养中，我们还发现氨基-f-Sc3N@C80和氨基-f-Gd3N@C80可减轻肿瘤坏死因子-α引起的神经炎症。综上所述，我们介绍了一种有效清除自由基、抗炎和镇痛的氨基功能化80碳金属富勒烯纳米粒子的体内外研究结果。我们的研究为开发多效性治疗策略来应对炎症提供了重要的资产，炎症是椎间盘退变和相关疼痛的重要病理标志。
Low back pain is the most common health problem with a prevalence of over 80% worldwide and an estimated annual cost of $100 billion in the United States. Intervertebral disc degeneration accounts for a major cause of low back pain. However, there is still a lack of safe and effective treatment to tackle this devastating condition. In this study, we synthesized four functionalized trimetallic nitride endohedral metallofullerenes (carboxyl-f-Sc3N@C80, carboxyl-f-Gd3N@C80, amino-f-Sc3N@C80, and amino-f-Gd3N@C80) and characterized them with X-ray photoelectron spectroscopy, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and UV–vis. Via electron paramagnetic resonance, all four metallofullerene derivatives possessed dose-dependent radical scavenging capabilities (hydroxyl radicals and superoxide anions), with the most promising radical scavenging properties shown in the amine functionalized C80 metallofullerenes. Both amino-f-Sc3N@C80 and amino-f-Gd3N@C80 at 1 μM significantly reduced lipopolysaccharide induced reactive oxygen species production and mRNA expressions of pro-inflammatory mediators (inos, tnf-α, il-1, and cox-2) in macrophages without apparent cytotoxicity through regulating activity of p38 MAPK, p65, and nuclear translocation of NF-κB. Furthermore, in an established mouse model of lumbar radiculopathy, amino-f-Sc3N@C80 and amino-f-Gd3N@C80 effectively alleviated ipsilateral mechanical hyperalgesia for up to 2 weeks. In dorsal root ganglia explant culture, we also showed that amino-f-Sc3N@C80 and amino-f-Gd3N@C80 ameliorated TNF-α elicited neuroinflammation. In summary, we presented results for a potent radical scavenging, anti-inflammatory and analgesic nanoparticle, amino-functionalized eighty-carbon metallofullerenes in vitro and in vivo. Our study provides important assets for developing pleiotropic treatment strategies to tackle the inflammation, a significant pathological hallmark in the intervertebral disc degeneration and associated pain.