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


聚乙二醇修饰的氧化铁纳米颗粒——高性能的磁共振造影剂

顾宁课题组建立了一种简单有效的方法制备聚乙二醇修饰的氧化铁纳米粒子。首先通过多个羧基与氧化铁纳米粒子的螯合作用,将聚丙烯酸(PAA)修饰到氧化铁纳米粒子表面,从而向氧化铁纳米粒子表面引入大量的羧基,再利用羧基与α,ω-二氨基PEG分子中一端氨基的反应,将PEG高密度的连接到氧化铁纳米粒子表面。该氧化铁纳米粒子具有良好的生物相容性和抗巨噬细胞吞噬能力。小鼠体内实验表明,PEG修饰可以有效降低氧化铁纳米粒子被肝脾组织摄取,从而实现其在肿瘤组织的有效富集,达到高效的磁共振肿瘤成像效果,该纳米粒子在磁共振肿瘤成像领域具有巨大的应用前景。
Dongfang Liu, Wei Wu, Jingjing Ling, Song Wen, Ning Gu,* Xizhi Zhang. Effective PEGylation of Iron Oxide Nanoparticles for High Performance in Vivo Cancer Imaging, Adv. Funct. Mater. 2011, DOI: 10.1002/adfm.201001658.


Fig.1 Schematic chemical structures of SPION-PAA, SPION-PEG and the synthetic route.


Fig.2 In vitro Prussian blue staining images of macrophages, RAW 264.7, after 2 h treatment with 0.6 mg Fe mL-1 of each SPIONs: SPION-PAA (a) and SPION-PEG (b).


Fig.3 T2*-weighted images (TR/TE of 408 ms/3.5 ms) at pre-injection and 4 h post-injection of 4 mg kg-1 of SPION-PEG (a), SPION-PAA (b) and Resovist (c) in the regions of the tumor on the proximal thigh, liver and spleen of the mice.


Fig.4 Ex vivo Prussian blue and nuclear fast red double staining images of tumor tissues excised from the mice untreated (a) and at 4 h post-injection of SPION-PEG (b), SPION-PAA (c) and Resovist (d) respectively.

包裹 Fe3O4纳米颗粒的微气泡在超声能量介导下对肿瘤细胞的作用研究

微气泡在较高声压(>0.1MPa)超声辐照下,由于剧烈的伸缩振动会发生破裂,导致微气泡周围的生物组织或细胞出现热效应、声穿孔或声辐照力等生物效应,这正是目前微气泡介导的超声无损治疗应用研究的基础。本研究以包裹 Fe3O4纳米颗粒(86.47μg/ml)的微气泡为模型,建立了微气泡与SMMC-7721肝癌细胞的体外超声实验。首先,通过控制超声辐照参数(1MHz频率,不同声强,相同辐照时间),评价了微气泡中的 Fe3O4纳米颗粒控制释放进入细胞的效率;然后,对被 Fe3O4纳米颗粒标记后的细胞进行了磁共振成像研究;最后,通过对微气泡超声辐照后的细胞进行SEM形貌观察,以及细胞内钙流变化情况实验,探讨了微气泡携带的 Fe3O4纳米颗粒在超声能量辅助下,进入细胞声穿孔方式和细胞发生的相关生物效应机理。
Fang Yang, Miao Zhang, Wen He, Ping Chen, Xiaowei Cai, Li Yang, Ning Gu, Junru Wu. Controlled Release of Fe3O4 Nanoparticles in Encapsulated Microbubbles to Tumor Cells via Sonoporation and Associated Cellular Bioeffects. Small 2011, 7(7), 902–910


Fig.5 SEM images of 7721 cells irradiated without US exposure in the presence of EMBs (A,A-1). After B,E) 0.1, C,F) 0.5, and D,G) 0.75 W cm -2 US exposure for 40 s with Fe3O4-NP-embedded microbubbles (B,C,D) and non-NP-embedded microbubbles (E,F,G). The B-1 to G-1 images are local enlarged magnifications of the corresponding group, in which the plasma membrane structure, the cytoskeleton, and the nanoparticles on the membrane (arrows) can all be clearly seen. The EDXA spectra after 0.5 W cm-2 US exposure for 40 s with non-NP-embedded and Fe3O4-NP-embedded microbubbles are shown in (H) and (I), respectively. The image in (I) clearly reveals that the cell interaction with Fe3O4-NP-embedded microbubbles after US exposure consists of Fe elements, except the C, N, O, Na, P, and S elements in image (H), which indicates the existence of Fe3O4 NPs in the cell structure.


Fig.6 Cell viability exposed to US depends on the cell-cycle phase.


Fig.7 The Fluo-3 fluorescent intensity changes after US (0.1, 0.5, 0.75 W cm-2) and microbubbles treatment.