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Papers: 14 May 2022 - 20 May 2022

2022 May 16

ACS Appl Bio Mater

Amine Functionalized Trimetallic Nitride Endohedral Fullerenes: A Class of Nanoparticle to Tackle Low Back/Leg Pain.


Xiao L, Huang R, Sulimai N, Yao R, Manley B, Xu P, Felder R, Jin L, Dorn HC, Li X
ACS Appl Bio Mater. 2022 May 16.
PMID: 35575694.


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-ScN@C, carboxyl-f-GdN@C, amino-f-ScN@C, and amino-f-GdN@C) 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 metallofullerenes. Both amino-f-ScN@C and amino-f-GdN@C at 1 μM significantly reduced lipopolysaccharide induced reactive oxygen species production and mRNA expressions of pro-inflammatory mediators (, , , and ) 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-ScN@C and amino-f-GdN@C effectively alleviated ipsilateral mechanical hyperalgesia for up to 2 weeks. In dorsal root ganglia explant culture, we also showed that amino-f-ScN@C and amino-f-GdN@C 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 and . 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.