期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 42, 页码 38405-38416出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b11783
关键词
intervertebral disc degeneration; low back pain; targeted therapy; fullerene; formyl peptide receptor-1
资金
- US NIH NIAMS [R0IAR064792, R21AR057512]
- Commonwealth Health Research Board (CHRB)
- North American Spine Society (NASS)
- Department of Orthopaedic Surgery at the University of Virginia
- Orthopaedic Trauma Association
Intervertebral disc degeneration associated back pain is the most common cause of disability worldwide; however, no safe and effective treatments 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-C-60) was synthesized by conjugating carboxyl-C-60 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-C-60 demonstrated preferential binding to FPR-1 on activated macrophages and significantly attenuated mRNA expressions of proinflammatory factors including interleukin-6, interleukin-1, tumor necrosis factor-alpha, and cyclooxygenase-2. In vivo animal studies exhibited that a single intravenous injection of FT-C-60 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 the mouse spine confirmed the targeting property of FT-C-60 toward the injured disc on POD 14. Quantitative analysis of histological staining on spine sections showed that nanoparticle FT-C-60 dramatically reduced inflammation at the 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.
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