Treatment of disc degeneration by nano-fullerenes

描述(申请人提供)：有症状的腰椎间盘退行性变似乎是慢性腰痛最常见的原因之一。虽然包括手术切除和组织工程在内的治疗技术已经被应用/提出，但对于临床医生和基础科学家来说，椎间盘退变的治疗仍然是一个巨大的挑战。氧化应激被认为在椎间盘退变过程的早期阶段起着重要作用。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，尤其是关于富勒烯及其衍生物对椎间盘退变的影响的报道还没有发表。本项目的目的是表征一种特定的富勒烯C60衍生物双甲基磷酸盐富勒烯(BMPF)的水溶液在体内外对椎间盘退变的抑制作用，该假说是基于它们可能在治疗椎间盘退变方面非常有效的假设。富勒烯及其衍生物包括BMPF和C60、一种单甲烷磷酸盐富勒烯、一种富勒醇和两种羧基富勒烯，将制备水性纳米颗粒悬浮液。研究其对过氧化氢或白介素1诱导培养的人视盘细胞凋亡和基质破坏的保护作用。通过兔环针模型进一步评价其对椎间盘退变的抑制作用。这项涉及化学、材料科学和生物医学的研究将为椎间盘退变的治疗策略提供有用的线索，并可能导致一些新的潜在候选治疗椎间盘退变。 与公众健康相关：富勒烯衍生物双甲烷磷酸盐富勒烯的纳米水悬浮液将通过不同的方法制备，并将在体外和体内研究它们对椎间盘细胞凋亡和基质破坏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.