【作者】 王友法；

【导师】 闫玉华；

【作者基本信息】 武汉理工大学 ， 材料学， 2005， 博士

【摘要】 纳米粒子由于其纳米效应而表现出许多既不同于宏观物质也不同于单个孤立原子的特异性能,这些特异性能使得纳米粒子具有许多新的用途。论文就生物医用纳米磷灰石溶胶的制备、表征、纳米颗粒形貌和尺寸控制及纳米磷灰石溶胶稳定性研究等方面展开研究。主要目的是获得尺寸均匀稳定、分布范围窄的纳米磷灰石,获取指定形貌的磷灰石系列纳米粒子,寻找合适的稳定剂,并研究纳米粒子在水中的分散特性及溶胶的稳定特性及稳定机理,在此基础上研究纳米磷灰石的部分纳米生物学效应。 论文利用均相共沉淀法、水热反应法和酸碱中和法制备出羟基磷灰石、含锶磷灰石和锶磷灰石三种磷灰石纳米粒子溶胶。实现了磷灰石纳米粒子粒径和粒径分布的控制合成。一方面可以根据需要合成平均粒径在20nm～100nm范围的任意尺度的磷灰石纳米粒子溶胶:另一方面可以获得粒子粒度分布范围窄的纳米粒子。 实现了磷灰石纳米粒子形貌的控制合成。利用透射电镜和原子力显微镜表征了控制生长的纳米磷灰石,粒子呈近似球形,粒子形貌均匀并且粒度分布范围窄。平均粒径为75.7nm的磷灰石颗粒中最大粒子与最小粒子粒径差为15.8nm,粒径偏差仅为10%。 通过控制合成得到的纳米羟基磷灰石晶体的c轴被拉长而a、b轴变短。晶格参数的变化使得晶体沿c轴方向的优先生长得到抑制,粒子生长成非针状磷灰石;对磷灰石而言,c轴被拉长意味着Ca²+与【PO₄】四面体的O²-距离更长,Ca2²+因而具有更高的活性,这种活性是纳米磷灰石特有的生物学效应的结构基础。同时也使磷灰石具有更高的反应活性。纳米掺锶磷灰石和锶磷灰石的晶格参数也被明显改变。 研究发现随着锶离子对钙离子的取代量的增加,磷灰石红外光谱上OH^-在高波数的伸缩振动光谱的谱带强度减弱,同时,吸收谱带向高波数方向漂移,漂移量的大小也存在规律性。这是由于磷灰石中锶离子半径大于被它所取代的钙离子的离子半径,导致OH^-红外吸收谱带的波数上升,反映了磷灰石中氢键OH…O的距离在增加。锶离子在磷灰石中的掺入对[PO4]四而体的P-O键亦产生更多还原

【Abstract】 The dimensions of nanoparticles range from 1 to 100 nanometers in diameter. Nanoparticles are capable of many properties that are different from both macroscopic materials and microscopic single atoms due to nanoeffects. This dissertation studies on preparation and characterization of nano apatite sol for biomedical applications, controllable growth of nanoparticles and stability mechanism of nano apatite sol. The goals of these studies are to obtain apatite nanoparticles whose dimensions fall into a narrow scope, to realize the controllable synthesis of apatite particles and to search suitable stabilizer of the sol. The dispersion characteristics of apatite nanoparticles and stability mechanism are studied in the dissertation. Some biomedical nanoeffects of apatite nanoparticles are discussed as well.Hydroxyapatite, strontium-containing apatite and strontium apatite are prepared through homogeneous co-precipitation method, hydrothermal method and acid-base neutralization titration method. The size and size distribution are controllable in the preparation process. Apatite nanoparticles with given size could be obtained when the desired mean diameter of particles is between 20 nanometers and 100 nanometers. Furthermore, the size distribution scope could be very narrow. For instance, among those particles with 75.7 nanometers as mean diameter, the dimension difference between the smallest particle and the biggest one is less than 16 nanometers. The diameter deviation among particles is 10% only.It is realized to controllably synthesize apatite nanoparticles in given morphology. Transmission electron microscope and atomic force microscope are applied to study the particles. The hydroxyapatite particles are spherical grains. All particles are nearly the same in morphology and size.The c axis of the gained hydroxyapatite is elongated while a, b axis are shortened. The growth priority along c orientation is restrained by these changes of crystal lattice parameters. The grains do not grow in needle-like shape. For apatite, the elongation of c axis means the distance between Ca²+ and O²- in tetrahedral [PO₄]becomes longer. Thus the Ca2+ ions are more active in reaction. The reaction activity is the structure base of bioeffects of nano apatite. It enables apatite higher activity. The crystal lattice parameters of strontium-containing apatite and strontium apatite are also distinctively altered.With increasing of strontium ions substitution for calcium ions in apatite, the absorption band of hydroxyl group shifts towards high wave numbers. There is regularity between the shift and cation substitution. The wave number of OH’ band increases with an increase in the radii of cations of hydroxyapatite owing to the increase in hydrogen bond distance OH--O. The doping of strontium cation in apatite also has effects on P-0 bond in [PO4] tetrahedron. The wave number of PO43" band decreases with an increase of substitution of strontium cations for calcium cations in hydroxyapatite crystals. The shift direction of phosphate anion bang is opposite to that of hydroxyl group band. The array and orientation of [PO4] tetrahedron are affected by the doping of strontium cations; and the length of P-0 bond is changed by them too. These effects result in diversity of physicochemical and biological characteristics of three kinds of apatite.The surface elements and their distribution of nano apatite are studied by Auger electron spectrum and energy dispersive spectrum. The qualitative analysis of Auger electron spectrum about surface elements reveals that no special elements are accumulated or segregated. The energy dispersion spectrum indicates that there are calcium vacancies in the crystal structure of nanoparticles. The hexagonal symmetric lattice is modified so spherical grains form. The deficiency of calcium on surface lowers the stability of the crystal surface which results in high reaction activity.Specific surface of nanoparticles are measured by nitrogen adsorption method. The BET specific surface area of nano apatite is more than 150 square meters per gram while Langmuir specific surface area is higher than 250 square meters per gram. That means there are nearly 20% of all atoms on the apatite nanoparticles’ surface. Apatite nanoparticles thus possess high surface effect.Solubility study on nano hydroxyapatite reveals that there is big difference between nano hydroxyapatite and normal block hydroxyapatite in solubility. The pKsp value of nano hydroxyapatite is about 75. That is quite different from the knownvalue-117 of hydroxyapatite. It is even slightly lower than that of amorphous calcium phosphate. It shows great difference between dissolution properties of nano hydroxyapatite and that of block hydroxyapatite. The solubility and dissociation degree of nano hydroxyapatite are much higher than those of block hydroxyapatite.The aquatic dispersion specialties of apatite nanoparticles are also discussed in the dissertation. The Zeta potential of the sol system is a token of the stability. The effects of stabilizer and its concentration on surface potential are studied. The dissertation gives deep discuss about variation trend of enthalpy-entropy when stabilizer exists. The adsorption model of stabilizer A on apatite surface is established capitalizing on surface Auger electron spectrum. Stabilizer’s existence creates interspace steric effects and osmotic pressure effects. These effects make the sol system stable. The discussed stability mechanism is used as theory to select other kinds of stabilizer.Some bioeffects of three kinds of nano apatite are studied. Human liver cancer cells and normal hepatic cells are treated by three kinds of apatite nanoparticles. Synchrotron radiation X-ray fluorescence analysis is used to detect the content variation of calcium and phosphor elements in cancer cells when the cells are treated by hydroxyapatite nanoparticles. Experiments verify that the contents of calcium and phosphor elements in hepatocellular carcinoma have obvious increases after the cells are treated by hydroxyapatite nanoparticles. And the contents increase with hydroxyapatite concentration and treatment time increasing. The Ca/P molar ratio in treated cell is different from both that in hydroxyapatite and that in untreated cancer cell. Apatite nanoparticles evidently alter the calcium and phosphor environments in treated hepatocellular carcinoma cells. That finally halts the proliferation of carcinoma cells.更多还原