多羧基小分子在生物磷灰石矿化过程中的介入及仿生矿化实验研究

Bioapatite is one kind of biogenic minerals which are intimately related to human life and health. In general, apatite imbedded in the bone of vertebrate presents plate-like morphology at nanometer level. Polycarboxylic small organic molecules, especially citrate, have been identified as having prominently synergistic effect in the bioapatite nanocrystals dimensional controls. However, it is inexplicable in which periods these small organic molecules get involved in the dimensional controls during the bioapatite nanocrystals formation. In this project, the apatite crystals which were separated from different age Danio rerio (Zebrafish) tail fins are intended as a model mineral of apatite. Through the systematically characterization of the composition, microstructure and assembly structures of apatite minerals, the mineralogical feature of this type of apatite mineral in in-vivo evolution is desired to be revealed clearly. By analyzing the citrate content, citrate embedded distribution and the interaction of citrate with apatite nano-plates in different apatite formation durations, the specific intervention duration and the possible intervention mechanism of citrate into apatite mineral are prospectively to be illuminated. Simultaneously, the study of biomimetic mineralization of apatite in the presence of model polycarboxylic small organic molecules will be carried out. An integrated and dynamic in-vivo mineralization process model of apatite will be hopefully established based on the results of above research. The smooth implementation of this project may conduce to deepen the understanding of the biogenic apatite mineral formation process, further developand enrich the current biomineralization theory, and expand the scope of application of biomineralization theory in the field of mineralogy, palaeontology, biomedical engineering and biomimetic materials science as well.

生物磷灰石是一类与人类生命活动和健康息息相关的生物矿物。脊椎动物骨骼中的磷灰石一般呈现纳米尺寸的片状结构。多羧基有机小分子尤其是柠檬酸根已被确认对生物磷灰石晶体的尺寸控制存在显著的协同作用；但该类分子在磷灰石哪一个具体形成阶段介入了晶体的尺寸控制却一直令人费解。本项目试图以不同年龄段斑马鱼尾鳍骨中的磷灰石为模型矿物，通过对磷灰石矿物的组成、微结构和组装结构进行详细分析，揭示该类磷灰石体内演化的矿物学特征；通过分析柠檬酸根在磷灰石形成的不同阶段的含量、嵌入分布以及与矿物的结合情况，阐明该类小分子在磷灰石形成过程中具体介入阶段和可能的介入机制；结合多羧基小分子参与的磷灰石仿生矿化实验研究，建立一个完整动态的磷灰石体内矿化过程模型。项目的顺利实施有助于深入了解该类生物磷灰石完整的体内矿化过程，进一步丰富和发展生物矿化理论，拓展生物矿化理论在矿物学、古生物学、医学工程和仿生材料学等领域的应用范围。

在脊椎动物骨骼组织形成过程中，生物分子尤其是多羧基小分子在诱导无机矿物的有序成核、结晶和生长等方面发挥着极其重要的作用，特别是调控形成硬组织的有序孔结构。但其中的机制一直令人费解。本项目通过在介孔羟基磷灰石的表面浸渍涂布多羧基小分子柠檬酸，利用一系列分析技术特别是SSNMR技术对羟基磷灰石和多羧基小分子的结合情况开展了研究，初步揭示了羟基磷灰石和多羧基小分子在分子层面的作用。以此为基础，制备了一种对重金属离子具有较好交换吸附效果的多孔羟基磷灰石材料，同时制备了一种纳米羟基磷灰石复合物颗粒，该复合材料具有新颖的核-壳结构和较大的比表面积，展现了对有机污染物较好的吸附去除效率，目前正开展该材料和一些高分子材料的复合研究，并期望用于制备污水处理相关器件。受上述介孔羟基磷灰石研究的结果启发，我们进一步选择对生物体具有较好相容性的金属离子和有机配体，获得了一种生物相容良好的gefitinib@ZIF-8纳米药物，该药物对非小细胞肺癌细胞展现了较好的定向毒性作用，有望用于特定肿瘤细胞的靶向治疗。受项目资助，课题研究已发表了相关科研论文6篇，另有3篇研究论文在投稿中，申报了专利2项，培养了3名硕士研究生，安排了3人次参加了国际国内相关学术会议。