水溶性富勒烯材料增强细胞活性的生物效应与作用机制研究

Fullerene derivatives have great potential in biomedical applications such as anti-oxidative damage and tumor therapy. Our previous investigation shows that water-soluble fullerene materials are able to enhance the viability of cell. As a result, research focused on the biological effect and mechanism that water-soluble fullerene derivatives enhanced cell viability is of great significance to promote their further applications in biomedicine. In this project, a series of water-soluble fullerene derivatives with different types of surface charges will be prepared, their structures and properties will be characterized and labeled with fluorescence marker. Then their capability of cell viability improvement will be investigated for the determination of the minimum effective and safe concentrations, while the influence on cell proliferation and cell cycle will also be studied to reveal the roles they played on cell growth and differentiation, which can provide theoretical foundation for the clinical safety evaluation on water-soluble fullerene materials. In order to clarify the effect of surface charges of fullerene materials on regular cellular uptake and intracellular distribution behavior, the mechanism of cellular uptake on water-soluble fullerene materials and the subcellular localization of them will be investigated intensively, and transcriptome sequencing and digital gene expression profiling analysis will be performed to elucidate the molecular biological mechanism that water-soluble fullerene materials conducted on the cell viability, so obtained results will provide a valuable theoretical basis for supporting and expanding the biomedical applications of fullerenes.

富勒烯材料在抗氧化损伤、肿瘤诊疗等生物医学领域具有重大应用前景，前期研究发现，水溶性富勒烯材料能够增强细胞活性。因此，系统研究水溶性富勒烯材料增强细胞活性的生物效应与生物作用机制，对进一步推进富勒烯材料在生物医学领域的应用具有重要意义。本项目拟设计合成系列具有不同类型表面电荷的水溶性富勒烯衍生物，并对其进行结构性质表征和荧光标记；然后系统地研究其增强细胞活性的生物效应，确定起效浓度与安全浓度范围；通过深入探索其对于细胞增殖和细胞周期的作用机制，获得其对细胞生长、分化等的影响规律，为富勒烯材料的临床安全性评价提供基础支撑。在此基础上，通过系统研究水溶性富勒烯材料的细胞摄取机制、亚细胞定位，结合转录组测序和数字基因表达谱测序分析筛选等，期望阐明其表面电荷对于细胞摄取和细胞内分布行为的影响规律及其增强细胞活性的分子生物学机制，为支撑和拓展富勒烯的生物医学应用提供有价值的理论研究基础。

水溶性富勒烯材料在抗氧化损伤、肿瘤治疗、化疗保护等疾病防治领域具有重大应用前景，并且在生物安全性方面表现出显著的优势。研究水溶性富勒烯材料对机体正常细胞的生物效应及其生物作用机制，对于评价其在临床应用中的安全性和加快推进其生物医学应用发展具有重要意义。本项目设计合成了具有相同分子构型的正电性氨基富勒烯（C60-EDA）和负电性羧基化富勒烯（C60-(EDA-EA)），两者均具有优异的水溶性和活性氧清除能力。正电性的C60-EDA通过与细胞膜的静电相互作用和大胞饮机制被细胞快速摄取，富集在线粒体和溶酶体中，而负电性C60¬-(EDA-EA)主要聚集在溶酶体中。并且，C60-EDA在低浓度下能够显著增强正常细胞活性和促进细胞增殖，转录组学分析显示其可能通过转录后调控机制影响细胞活性和细胞增殖。本项目通过比较不同表面电荷的水溶性富勒烯衍生物对细胞摄取、亚细胞分布、细胞活性和细胞增殖的调控作用，揭示了表面电荷对其生物活性的影响规律，为富勒烯材料的生物医学应用提供了基础支撑和新策略。