国家重大科学研究计划项目“生物医学纳米材料对血细胞作用的研究”工作进展与讨论

结合多模态纳米探针进行淋巴癌等血液恶性肿瘤的在体分子成像与疗效评价研究

东南大学 顾宁 教授


氨基葡萄糖修饰的氧化铁纳米粒----肿瘤靶向磁共振对比剂

通过氨基脱氧葡萄糖与DMSA包覆的氧化铁纳米粒反应,将脱氧葡萄糖(DG)标记到磁性纳米粒表面,从而实现了靶向高表达葡萄糖受体的恶性肿瘤细胞,为肿瘤靶向成像开辟了新的途径。
Xiu Hong Shan, Hui Hu, Fei Xiong, Ning Gu, Xin Dong Geng, Wei Zhu, Jiang Lin and Ya Fei Wang. Targeting Glut1-overexpressing MDA-MB-231 cells with 2-deoxy-D-glucose modified SPIOs. European Journal of Radiology, 2011, DOI:10.1016/j.ejrad.2011.03.013.


Fig. IR of γ-Fe2O3@DMSA NPs (a) and γ-Fe2O3@DMSA-DG NPs (b):1107 cm-1 corresponds to C-N stretching vibration,indicate that 2-DG is bound to the surface of γ-Fe2O3@DMSA NPs.


Fig. Prussian blue-stained and nucleus fast red–counterstained MDA-MB-231 cells incubated with γ-Fe2O3@DMSA NPs (A-D), γ-Fe2O3@DMSA-DG NPs (E-H), and γ-Fe2O3@DMSA-DG NPs + anti-Glut1 (competition; I-L) at an iron concentration of 25 µg/ml of nonglucose medium for different time intervals (10 min, 20 min, 1 h, and 2 h). Control cells that were not incubated with particles are shown in (M). Higher uptake of γ-Fe2O3@DMSA-DG NPs (blue granules) compared with γ-Fe2O3@DMSA NPs and γ-Fe2O3@DMSA-DG NPs competed with anti-Glut1 is clearly indicated.

多层介电-金属金纳米壳光学性质及FANO效应的研究

金属纳米材料中的局域表面等离激元具有许多特殊的光学性质,有着非常广泛的应用前景,是当今纳米科学研究中的一个热点。当纳米颗粒之间非常接近的时候,其相互之间的近场耦合作用会强烈的影响系统的光学特性,我们使用电磁散射理论研究了多层纳米壳链状结构的光学性质。

首先我们建立了一种通用的基于米氏(Mie)理论的多层多粒子光学散射的全解析方法,该方法能够精确的对包含任意多个同心球形粒子的系统的近场和远场光学响应进行求解。同时我们采用有限元方法的验证了程序的正确性,相比于数值方法,该方法能够大大的减少计算资源和时间。我们使用该方法计算了制备方法比较成熟的金硅金三层纳米壳的光学性质,分析了多层纳米壳中不同模式的等离激元的耦合机制。当金壳层和金核的等离激元的震荡相位相同的时候,系统的吸收和散射大大增强,我们称之为“明模式”;当金壳层和金核的等离激元的震荡相位相反的时候,会强烈的抑制散射,我们称之为“暗模式”。和原子物理中的FANO效应相似,“明模式”和“暗模式”的耦合会导致不对称的消光峰。最后我们计算了一维金属纳米壳链状结构的近场和远场响应,分析了近场耦合对“暗模式”的影响以及电磁增强效应,结果表明近场耦合效应使“明模式”的光谱峰变宽并且红移,但是对“暗模式”的影响很小,并且在“暗模式”波长下,电场增强达到最大。
Meng Wang, Min Cao, Xin Chen, and Ning Gu, Subradiant Plasmon Modes in Multilayer Metal-Dielectric Nanoshells, J. Phys. Chem. C, 2011, 115 (43), pp 20920-20925


Fig. Comparison of the calculated extinction and near-field results of GMM theory and FEM. (a) Extinction efficiency of a R20/30/40/50 nm Au@SiO2@Au@SiO2 MNS dimer with interparticle spacing of 5 nm. Local electric fields in the x-y plane plotted in logarithmic scale calculated from FEM (b) and GMM theory (c) at the dipolar resonance wavelength (λ = 1010 nm).


Fig. Extinction efficiencies of R25/30/50 nm Au@SiO2@Au MNS chains. MNSs aligned normal (a) and parallel (b) to the polarization with different particle numbers (d = 10 nm). (C) MNSs aligned parallel to the polarization with different spacings (N = 10). (d) MNS chain embedded in mediums with different refractive indices (N = 10, d = 10 nm). The dashed line corresponds to a single Au@SiO2@Au MNS.


Fig. Far- and near-field optical properties of a R25/30/50 nm Au@SiO2@Au MNS chain (N = 10, d = 10 nm). Optical cross sections (a), surface charge distributions (b), and electric field intensities (c) are plotted. The dashed lines in (a) correspond to a solid gold nanoparticle chain.

微纳热电偶探测细胞内温度的研究

细胞是生命体的最小结构和功能的单位,细胞的生长、分裂、新陈代谢, 都从一个侧面反应生命体的生命状态和健康程度。而在这些生命过程中,伴随着物质转移和能量的转化,因此细胞内局部的温度可能会发生微小的变化。为了检测这一微小的温度信号变化,我们设计制作了微纳热电偶测温探针,其seebeck系数为4.6μV/K~10.2μV/K, 通过模拟得到探针的热响应时间约为400ns。

我们将探针插入U251脑胶质瘤细胞内并对其进行温度探测,使用两种抗癌药物喜树碱和阿霉素对细胞进行刺激,并在喜树碱组中探测到温度上升,以及上升过程中温度剧烈的变化。而在阿霉素组中却未发现温度上升。这一差别很可能是由于两种药物作用机理不同导致,因此监测细胞对药物刺激时温度的变化,有可能为药物筛选提供新的研究方法。
Changling Wang, Ruizhi Xu, Wenjuan Tian, Xiaoli Jiang, Zhengyu Cui, Meng Wang, Huaming Sun, Kun Fang and Ning Gu, Determining intracellular temperature at single-cell level by a novel thermocouple method, Cell Research (2011) 21:1517-1519


Fig. (A) SEM image of tungsten probe coated by polyurethane (PU; except at the tip which is uncoated). (B) SEM image of the thin platinum film as an outermost layer. (C) Curves of the thermoelectric power from 0 °C to 90 °C. Red, green, and blue curves represent the thermoelectric power of the regular bulk W-Pt thermocouple, TC probe with 100-nm thick Pt film, and TC with 50-nm thick Pt film, respectively. (D) Optical microscopic image of a living U251 cell inserted by the TC probe. (E) A column figure indicating the average temperature changes for total cells after two drug treatment. (F) The simulated results of the TC probe response to a cell 2 °C higher than the environment. (G) Upper panel, a typical curve showing the changes of the intracellular temperature of a single U251 cell after CPT treatment. (a) TC inserted into the cell, (b) addition of CPT, and (c) TC withdrawn from the cell. Lower panel, a typical curve showing no temperature changes after addition of DOX. (a) TC inserted into the cell, and (b) addition of DOX. (H) A higher-resolution plot of part of the curve shown in (G) upper panel.