金核壳纳米粒子的控制合成及其生物复合(英文)

合成了一系列Au/SiO2核壳纳米粒子,并详细研究了Au纳米壳层的生长过程。发现在金纳米壳层形成的过程中存在着2个竞争反应。利用这一发现,可将金纳米壳层的吸收峰从524nm连续调谐至980nm处。恩度是一种临床抗癌药物,我们首次将其生物复合于吸收峰位于808nm的Au/SiO2壳层表面,得到Au/SiO2-Endo,通过FTIR测试证明该生物复合成功。将恩度特殊的饿杀肿瘤特性以及对肿瘤具有特异识别能力,与Au/SiO2纳米壳层结构的光学可调谐特性以及良好的光热转换能力复合于一体,我们期望得到一种治疗肿瘤效果更强的新型药物。     

SiO2 /Au核壳结构纳米粒子的制备及表征

通过以金纳米粒子为表面晶种和壳生长的方法制备了金纳米壳包覆二氧化硅的复合纳米粒子。采用TEM 和UV-Vis对复合粒子进行了表征和研究，结果表明所得到的复合粒子粒径均匀、金纳米壳光滑完整，且壳厚度可通过反应物的用量来控制。当核半径与壳厚度之比在4到13之间变化时,复合粒子的光学共振峰在可见光区到近红外光区范围内可发生大于500 nm波长的移动。     

Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice

Clinical studies have been carried out for detailed measurements of the build-up and clearance of engineered gold nanoshell in the tissues of dosed mice. These optically tunable nanoshells are under consideration for a new therapy for tumors. The proposed therapy would involve the injection of the nanoshells and their preferential accumulation in tumor sites. This will be followed by irradiation with a monochromatic near infrared laser, which will induce cellular hyperthermia, thereby eradicating the tumor. Neutron activation analysis has been used for the detection and quantitation of gold, and therefore, the nanoshells, in dosing materials, blood, bones and other tissues as well as tumors at varioius sacrifice times following dosing. Feasibility studies have shown instrumental neutron activation analysis to be uniquely suited for detection of the gold nanoshells over a wide dynamic range. This allows for the study of high concentrations of gold in tissues which scavenge the shells from the blood (liver, spleen, kidney) as well as for much lower concentrations in those which do not (muscle, brain). In particular, the tissues from animals sacrificed after the longest post dose delay (28 days) and the control animals required experimental optimization to ensure the lowest possible determination limits. The mass of gold in the tissue samples ranged from our determination limit (about 70 pg) to a few micrograms.     

金纳米壳球体的制备及其潜在的生物学应用

利用分子自组装和胶体还原化学制备出具有核-壳结构的金纳米壳球体Au@SiO₂; 通过透射电子显微镜(TEM)、X射线光电子能谱 (XPS)和紫外-可见分光光度计对Au@SiO₂的制备过程及其在全血中的光学特性进行了研究. 结果表明, 通过改变复合颗粒Au-APTES-SiO₂的浓度, 可以得到具有合理核-壳比例的Au@SiO₂, 其等离激元共振峰位于光谱的近红外区, 这使得具有红外消光特性的金纳米壳球体具有潜在的生物学应用价值.     

Evolution of ultrafine gold seed nanoparticles with temperature and time and synthesis of plasmonic nanoshells

Features of the evolution of ultrafine gold nanoparticles synthesized by the Duff method with temperature and time have been studied in relation to their use as seeds for the formation of plasmonic nanoshells. A quantitative relation has been revealed between the duration of preheating of such particles at a preset temperature and their size. The obtained relation indicates that Au nanoparticles grow mainly via the Ostwald ripening mechanism. Using anisotropic composite FeOOH/Ag particles as an example, it has been shown that the obtained information may be used to substantially decrease the duration of the synthesis of metal nanoshells on diverse cores.     

Au和SiO2多壳结构的制备和表征

利用自组装技术和胶体还原化学, 制备出金纳米壳Au@SiO₂以及SiO₂包裹的金纳米壳SiO₂@Au@SiO₂; 去除SiO₂@Au@SiO₂颗粒中的金壳层, 获得含有可移动SiO₂核的空心壳H-SiO₂@M-SiO₂. 结果显示: SiO₂@Au@SiO₂复合颗粒表面光滑, 并保留了金壳的近红外吸收特性; 通过改变复合颗粒外层SiO₂厚度, 可以调节其等离激元共振峰的位置; 王水可以有效地去除SiO₂@Au@SiO₂中的金壳, 相应的等离激元共振峰消失.     

Chip-based SALDI-MS for rapid determination of intracellular ratios of glutathione to glutathione disulfide

Alterations in the ratio of glutathione(GSH) to glutathione disulfide(GSSG) reveal the cell living state and are associated with a variety of diseases. In this study, an Au NPs grafted nanoporous silicon chip was used for surface assisted laser desorption ionization-mass spectrometry(SALDI-MS) detection of GSH. Due to the bond interaction between thiol of GSH and Au NPs modified on the chip surfaces, GSH could be captured from the complex cellular lysate. Meanwhile, the composite nanostructures of Au NPs grafted porous silicon surface presented good desorption/ionization efficiency for GSH detection. The GSH levels in different tumor cells were successfully detected. Chip-based SALDI-MS was optimized for quantification of intracellular GSH/GSSG ratio changing under drug stimulation in liver tumor cells, GSSG was reduced to GSH by reductant of tris(2-carboxyethyl)phosphine(TCEP) and isotope-labeling GSH was as an internal standard. It was found that the increasing concentration of drug irinotecan and hypoxia culture condition caused the rapid consumption of GSH and a decrease of GSH/GSSG ratio in liver tumor cells. The developed SALDI-MS method provided a convenient way to accurately measure and rapidly monitor cellular GSH value and the ratios of GSH/GSSG.     

Preparation of Silver Nanoshells on Silica Particles by a Simple Two-step Process

A simple two-step method was developed to prepare silver nanoshells coated on silica paticles. The method involves two steps: concentration of reaction precursor (AgNO3) on particle surfaces and subsequent reduction by formaldehyde. The obtained composite particles were characterized by TEM, ED, and SEM-EDS measurements. The results show that the silver nanoshell is coated on silica particle surface in the form of a polycrystalline (cubic structure) layer with average thickness of 20 nm and weight percentage of 1.9%.     

生物降解高分子胶束-金壳纳米结构的制备和性能研究

聚己内酯-聚赖氨酸嵌段共聚物(PCL-b-PLys)在水中自组装形成了聚赖氨酸为壳和聚己内酯为核的球形胶束.以胶束为模板,利用聚赖氨酸的胺基与金的配位作用,引导金在胶束壳层上生长,形成了胶束-金壳纳米结构(micelle@gold nanoshell).用紫外可见光谱、X射线光电子能谱、广角X射线衍射、透射电镜、动态光散射、热重分析、光热转化实验、以及体外光热杀死癌细胞实验等对金壳结构进行了结构确认和性能表征.胶束-金壳结构比原胶束增大约30%～40%,金约占总重量2/3.而且,其具有很强的近红外吸收性能和高达63%的近红外光-热转化效率.近红外激光照射10 min,可杀死约60%的宫颈癌细胞,且自身的细胞毒性低.     

General Formation of Macro-/Mesoporous Nanoshells from Interfacial Assembly of Irregular Mesostructured Nanounits

Mesoporous core–shell nanostructures with controllable ultra-large open channels in their nanoshells are of great interest. However, soft template-directed cooperative assembly to mesoporous nanoshells with highly accessible pores larger than 30 nm, or even above 50 nm into macroporous range, remains a significant challenge. Herein we report a general approach for precisely tailored coating of hierarchically macro-/mesoporous polymer and carbon shells, possessing highly accessible radial channels with extremely wide pore size distribution from ca. 10 nm to ca. 200 nm, on diverse functional materials. This strategy creates opportunities to tailor the interfacial assembly of irregular mesostructured nanounits on core materials and generate various core–shell nanomaterials with controllable pore architectures. The obtained Fe,N-doped macro-/mesoporous carbon nanoshells show enhanced electrochemical performance for the oxygen reduction reaction in alkaline condition.     

Spiky gold nanoshells

We report a high-yield synthetic method for a new type of metal nanostructure, spiky gold nanoshells, which combine the morphological characteristics of hollow metal nanoshells and nanorods. Our method utilizes block copolymer assemblies and polymer beads as templates for the growth of spiky nanoshells. Various shapes of spiky metal nanoshells were prepared in addition to spherical nanoshells by using block copolymer assemblies such as rod-like micelles, vesicles, and bilayers as templates. Furthermore, spiky gold shells encapsulating magnetic nanoparticles or quantum dots were prepared based on the ability of block copolymers to self-assemble with various types of nanoparticles and molecules. The capability to encapsulate other materials in the core, the shape tunability, and the highly structured surface of spiky nanoshells should benefit a range of imaging, sensing, and medical applications of metal nanostructures.     

Biodistribution and bioactivity of tetra-pegylated meta-tetra(hydroxyphenyl)chlorin compared to native meta-tetra(hydroxyphenyl)chlorin in a rat liver tumor model

It has been proposed that the construction of a photosensitizer-polymer conjugate would lead to an increased selective retention of the drug in tumor tissue resulting in an enhancement of selective tumor destruction by light in photodynamic therapy. In this study the kinetics of a tetra-pegylated derivative of meta-tetra(hydroxyphenyl)chlorin (mTHPC-PEG) were compared with those of native meta-tetra(hydroxyphenyl)chlorin (mTHPC) in a rat liver tumor model. In addition, the time course of bioactivity of both drugs was studied in normal liver tissue. Pegylation of mTHPC resulted in a two-fold increase in the plasma half-life time, a five-fold decrease in liver uptake and an increase in the tumor selectivity at early time intervals after drug administration. However, although mTHPC concentrations in liver decrease rapidly with time, mTHPC-PEG liver concentrations increased as a function of time. This led to a loss of tumor selectivity at all but the earliest time points, whereas with mTHPC tumor selectivity increased with time. For both drugs the time course of bioactivity in the liver parallels drug concentration levels with extensive necrosis after irradiation of mTHPC-PEG-sensitized liver tissue up to drug-light intervals of 120 h. It is concluded that on balance mTHPC-PEG does not appear to show any benefits over native mTHPC for the treatment of liver tumors, as normal liver tissue accumulates the compound. However, pegylation is a potentially promising strategy with an increase in tumor selectivity and reduced liver uptake if accumulation in the liver can be prevented.     

Vibrational modes of metal nanoshells and bimetallic core-shell nanoparticles

We theoretically study the spectrum of radial vibrational modes in composite metal nanostructures such as bimetallic core-shell particles and metal nanoshells with dielectric core in an environment. We calculate frequencies and damping rates of fundamental (breathing) modes for these nanostructures along with those of two higher-order modes. For metal nanoshells, we find that the breathing mode frequency is always lower than the one for solid particles of the same size, while the damping is higher and increases with a reduction in the shell thickness. We identify two regimes that can be characterized as weakly damped and overdamped vibrations in the presence of external medium. For bimetallic particles, we find periodic dependence of frequency and damping rate on the shell thickness with period being determined by the mode number. For both types of nanostructures, the frequency of higher modes is nearly independent of the environment, while the damping rate shows a strong sensitivity to the outside medium.     

Microstructure control of Zn/ZnO core/shell nanoparticles and their temperature-dependent blue emissions

The microstructure of the Zn/ZnO core/shell nanoparticles synthesized by laser ablation in liquid medium can be facilely controlled. With the surfactant concentration increased over the critical micelle concentration, the nanoparticle transformed from pure ZnO to a Zn/ZnO core/shell structure. Further, with a decrease of the applied laser power, the ZnO shell thickness was monotonously reduced till 2.5 nm and the ultrafine ZnO nanocrystals embedded in the nanoshells were also reduced till 1.5 nm, which induced the increase of the disorder degree of the nanoshell lattice. The controlling mechanism was discussed according to the competition of capping protection and the oxidation reaction of laser-induced plasma. Blue photoluminescence from the ZnO nanoshells was observed. The emission band exhibited abnormal red-blue shift and narrowing with increasing temperature. Such temperature-dependent behaviors can be well described by a localization model involving an interstitial zinc defect center. These results indicate that this method provides a convenient and universal way to obtain various metal/oxide core/shell nanoparticles with controllable microstructure, and it will be beneficial to an understanding of the physical origins of the blue emission in nanostructured ZnO as well as to extending its optical and electronic applications.     

用于卵巢癌化疗-光热联合治疗的吉西他滨/聚吡咯复合纳米粒子

利用铁离子诱发吡咯氧化聚合反应制备了尺寸均一的聚吡咯纳米粒子, 并进一步负载化疗药物吉西他滨, 得到了吉西他滨/聚吡咯复合纳米粒子. 该复合纳米粒子对吉西他滨的负载能力强, 在水溶液中的稳定性好, 有助于降低吉西他滨对正常组织的毒副作用. 此外, 该复合纳米粒子在近红外光区有较强的吸收, 能够将吸收的光能转化为热, 是一种良好的光热试剂, 具有光热治疗功能. 同时, 该复合纳米粒子能够在热刺激下释放吉西他滨, 具有光热介导的化疗功能. 因此, 吉西他滨/聚吡咯复合纳米粒子是一种兼具化疗和光热治疗功能的联合治疗试剂. 复合纳米粒子在808 nm近红外激光照射下能够快速提升系统温度, 实现光热治疗与化疗联合杀伤卵巢癌细胞, 具有良好的生物医学应用潜力.     

Fluorescent Metal Nanoshells: Lifetime-Tunable Molecular Probes in Fluorescent Cell Imaging

We reported the preparation of lifetime-tunable fluorescent metal nanoshells and used them as lifetime imaging agents for potential detection of multiple target molecules by a single cell imaging scan. These metal nanoshells were generated to have 40 nm silica cores and 10 nm silver shells. Three kinds of metal-ligand complexes tris(5-amino-1,10-phenanthroline)ruthenium(II) (Ru(NH(2)-Phen)(3) (2+)), tris(2,2'-bipyridine) ruthenium(II) (Ru(bpy)(3) (2+)), and tris(2,3-bis(2-pyridyl)pyrazine))ruthenium(II) (Ru(dpp)(3) (2+)) that have similar excitation and emission wavelengths but different lifetimes were respectively encapsulated in the cores of metal nanoshells for the purpose of fluorescence. Compared with the metal-free silica spheres, these metal nanoshells were found to display enhanced emission intensities and shortened lifetimes due to near-field interactions of Ru(II) complexes with the metal shells. The shortened lifetimes of these metal nanoshells were definitely unique relevant to the Ru(II) complexes: 10 ns for the Ru(Phen-NH(2))(3) (2+)-Ag nanoshells, 45 ns for the Ru(bpy)(3) (2+)-Ag nanoshells, and 200 ns for the Ru(dpp)(3) (2+)-Ag nanoshells. These lifetimes were longer than the lifetime of cellular autofluorescence (2 - 5 ns), so the emission signals of these metal nanoshells could be distinctly isolated from the cellular background on the lifetime cell images. Moreover, these lifetimes were also different from one another, resulting in the emission signals of three metal nanoshells could be distinguished from one another on the cell images. This feature may offer an opportunity to detect multiple target molecules in a single cell imaging scan when the metal nanoshells are bound with various targets in the cells.     

具有抗菌性能的载药复合微纳米纤维的制备及其结构和性能表征

利用静电纺丝技术制备了一种具有抗菌性能的氧化锌(ZnO)/聚乳酸(PLA)/聚己内酯(PCL)载药微纳米纤维膜,并通过扫描电子显微镜(SEM)、X射线衍射(XRD)和傅里叶变换红外光谱(FTIR)分别对复合膜的表面形态、元素组成和化学结构进行表征。通过抗菌实验评价了复合膜的抗菌性能,用紫外分光光度计测试复合膜在体外的药物释放行为。结果显示,以物理共混的方式将ZnO和氢溴酸高乌甲素(LAH)成功载入复合微纳米纤维;与PLA/PCL复合微纳米纤维膜相比,ZnO/PLA/PCL复合微纳米纤维膜表现出更好的抗菌效率。当ZnO含量为10%(wt)时,复合微纳米纤维膜具有最佳的抗菌性能;药物释放性能结果表明,ZnO/PLA/PCL复合微纳米纤维膜具有良好的药物缓释性能。     

一种简易合成具有近红外吸收的纳米金壳球体方法

对经典的合成方法进行了详细的系统性的研究,通过改变合成过程中各反应物的参数,简易地得到了稳定的具有近红外吸收的纳米金壳球体。利用紫外可见光谱、动态光散射仪和透射电镜研究了制备过程中的各个参数对纳米金壳球体光学性质的影响。实验结果显示胺化试剂的用量以及先导试剂的预处理等在制备过程中都是重要影响因素。由改进方法所制备的纳米金壳球体具有很窄的粒径分布,并能在没有外加表面活性剂的条件下稳定地单分散于水溶液中。这些方法的改进提供了一种简易制备具有近红外吸收的纳米金壳球体的方法,从而有利于拓展此类纳米粒子在生物医学领域中的应用研究     

Controlled texturing modifies the surface topography and plasmonic properties of Au nanoshells

We report a facile and controllable method for the postfabrication texturing of the surface topography of Au nanoshells based on site-selective chemical etching of the polycrystalline Au nanoshell surface by a bifunctional alkanethiol molecule, cysteamine. This nanoscale surface texturing process systematically introduces dramatic changes to the plasmonic properties of the Au nanoshells. The modification of the plasmon resonant properties of nanoshells as a function of increased surface roughness was examined experimentally and modeled theoretically using three-dimensional finite difference time domain (FDTD) simulations.