Amine Functionalized Trimetallic Nitride Endohedral Fullerenes: A Class of Nanoparticle to Tackle Low Back/Leg Pain.
Li XiaoRong HuangNurul SulimaiRicky YaoBrock ManleyPeng XuRobin FelderLi JinHarry C DornXudong LiPublished in: ACS applied bio materials (2022)
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-Sc 3 N@C 80 , carboxyl-f-Gd 3 N@C 80 , amino-f-Sc 3 N@C 80 , and amino-f-Gd 3 N@C 80 ) 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 C 80 metallofullerenes. Both amino-f-Sc 3 N@C 80 and amino-f-Gd 3 N@C 80 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-Sc 3 N@C 80 and amino-f-Gd 3 N@C 80 effectively alleviated ipsilateral mechanical hyperalgesia for up to 2 weeks. In dorsal root ganglia explant culture, we also showed that amino-f-Sc 3 N@C 80 and amino-f-Gd 3 N@C 80 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.
Keyphrases
- lipopolysaccharide induced
- quantum dots
- neuropathic pain
- anti inflammatory
- reactive oxygen species
- mouse model
- inflammatory response
- rheumatoid arthritis
- public health
- chronic pain
- oxidative stress
- traumatic brain injury
- lps induced
- magnetic resonance imaging
- computed tomography
- cell proliferation
- mental health
- ionic liquid
- cognitive impairment
- toll like receptor
- mass spectrometry
- social media
- hydrogen peroxide
- single molecule
- blood brain barrier
- dual energy
- postoperative pain
- health promotion