Treatment of disc degeneration by nano-fullerenes

描述（由申请人提供）：症状性椎间盘退变似乎是慢性腰痛症状的最常见原因之一。尽管包括手术切除和组织工程在内的治疗技术已被应用/提出，但椎间盘退变的治疗仍然是临床医生和基础科学家的巨大挑战。氧化应激被认为在椎间盘退变过程的早期阶段起重要作用。然而，在椎间盘退变的治疗中，使用抗氧化剂的治疗策略一直被忽视，特别是，没有关于富勒烯及其衍生物对椎间盘退变的影响的报道。 该项目的目的是表征特定富勒烯C60衍生物，双甲烷膦酸酯富勒烯（BMPF）的水溶液对椎间盘退行性变化的抑制作用，基于它们可能在椎间盘退变的治疗中非常有效的假设。水性纳米颗粒悬浮液将由富勒烯及其衍生物（包括BMPF和C60）、单甲膦酸酯富勒烯、富勒醇和两种羧基富勒烯制备。将研究它们对过氧化氢或IL-1诱导的培养人椎间盘细胞凋亡和基质破坏的保护活性。将使用兔纤维环针刺模型进一步评价它们对椎间盘退变的抑制作用。目前的研究涉及化学，材料科学和生物医学将提供有用的线索，椎间盘退变的治疗策略，并可能导致一些新的潜在候选人治疗椎间盘退变。 公共卫生相关性：将通过不同的方法制备富勒烯衍生物，双-甲烷膦酸酯富勒烯的水性纳米颗粒悬浮液，并且将在体外和体内研究它们对椎间盘中的细胞凋亡和基质破坏性变化的保护性氧化清除作用。

DESCRIPTION (provided by applicant): Symptomatic intervertebral disc degeneration appears to be one of the most prevalent causes of chronic low back symptoms. Although therapeutic techniques including surgical removal and tissue engineering have been applied/proposed, the treatment of disc degeneration still remains a great challenge to both clinical physicians and basic scientists. Oxidative stress is regarded to play an important role in the early stages of disc degenerative process. However, therapeutic strategies using antioxidative agents have been ignored in the treatment of disc degeneration, and in particular, there are no reports on the effects of fullerene and its derivatives on disc degeneration published. The aim of the project is to characterize the inhibitory effects of aqueous solutions of a specific fullerene C60 derivative, bis- methanophosphonate fullerene (BMPF) on degenerative changes of intervertebral disc in vitro and in vivo based on the hypothesis that they might be very effective in the treatment of disc degeneration. Aqueous nanoparticle suspension will be prepared from fullerene and its derivatives including BMPF and C60, a mono- methanophosphonate fullerene, a fullerol and two carboxyfullerenes. Their protective activities against apoptosis and matrix destruction of cultured human disc cells induced by hydrogen peroxide or IL-1 will be investigated. Their inhibitory effects on disc degeneration will be further evaluated by using a rabbit annulus needle puncture model. The present study involving chemical, materials science and biomedicine will provide useful clues to the therapeutic strategy of disc degeneration and possibly lead to some novel potential candidates for the treatment of disc degeneration. PUBLIC HEALTH RELEVANCE: Aqueous nanoparticle suspensions of a fullerene derivative, bis- methanophosphonate fullerene will be prepared by different methods and their protective oxidative scavenging effects will be investigated against apoptotic and matrix destructive changes in the intervertebral disc both in vitro and in vivo.