Ultrastructure of a Carbon Nanotube-based Delivery System for Cancer Therapy

用于癌症治疗的碳纳米管输送系统的超微结构

• 批准号: 7593843
• 负责人: Richard Leapman
• 金额: $ 1.59万
• 依托单位: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593843
• 关键词: Antineoplastic Agents; Binding; Biological Assay; Carbon; Carbon Nanotubes; Cell Nucleus; Cell Survival; Cells; Cisplatin; Cytoplasm; Data; Dehydration; Electron Microscopy; Electrons; Epidermal Growth Factor; Epithelial; Fluorescence Microscopy; Glutaral; Head and Neck Squamous Cell Carcinoma; Incubated; Individual; Malignant Epithelial Cell; Measurement; Nanotubes; Optics; Osmium Tetroxide; Pharmaceutical Preparations; Platinum; Resolution; Scanning Transmission Electron Microscopy Procedures; Subcellular structure; System; Therapeutic; Transmission Electron Microscopy; base; cancer cell; cancer therapy; epon; malignant mouth neoplasm; nanoparticle; research study; sample fixation; single walled carbon nanotube

We have performed ultrastructural experiments to investigate the application of functionalized carbon nanotubes to deliver therapeutic drugs to oral cancer cells. The anti-cancer drug cisplatin was covalently bound to single walled carbon nanotubes (SWNTs) and these were in turn bound to epidermal growth factor (EGF), which is expressed at very high levels by oral cancer cells. Cultured head and neck squamous cell carcinoma (HNSCC) cells of epithelial origin incubated with the functionalized nanoparticles were prepared for electron microscopy by fixation in glutaraldehyde and osmium tetroxide, followed by dehydration and embedding in epon. Electron micrographs, recorded digitally using a 120 kV TEM, revealed that bundles of SWNTs had entered the cells. In most HNSCC cells the SWNT bundles were distributed throughout the cytoplasm, whereas some cells showed a higher concentration of nanotubes adjacent to the cell nucleus. The results confirmed lower resolution data obtained from confocal fluorescence microscopy but provided more detailed information about the subcellular structures associated with the nanotubes after entry. Scanning transmission electron microscopy (STEM) and x-ray nanoanalysis are also being performed to characterize individual nanotubes and to determine the distribution of bound platinum atoms. The ultrastructural data are being correlated with optical measurements and cell viability assays conducted in NIDCR.

我们进行了超微结构实验，以研究功能化碳纳米管向口腔癌细胞递送治疗药物的应用。 抗癌药物顺铂与单壁碳纳米管 (SWNT) 共价结合，而单壁碳纳米管又与表皮生长因子 (EGF) 结合，而表皮生长因子 (EGF) 在口腔癌细胞中以非常高的水平表达。 与功能化纳米颗粒一起孵育的培养的上皮来源的头颈鳞状细胞癌（HNSCC）细胞通过固定在戊二醛和四氧化锇中，然后脱水并包埋在epon中，准备用于电子显微镜检查。 使用 120 kV TEM 数字记录的电子显微照片显示，单壁碳纳米管束已进入细胞。 在大多数 HNSCC 细胞中，SWNT 束分布在整个细胞质中，而一些细胞在细胞核附近显示出更高浓度的纳米管。 结果证实了从共焦荧光显微镜获得的较低分辨率数据，但提供了有关进入后与纳米管相关的亚细胞结构的更详细信息。 扫描透射电子显微镜 (STEM) 和 X 射线纳米分析也正在进行中，以表征单个纳米管并确定结合的铂原子的分布。 超微结构数据与 NIDCR 中进行的光学测量和细胞活力测定相关。