Department of Chemistry, University of Connecticut, Storrs, CT, USA.
Nanomedicine (Lond). 2010 Dec;5(10):1535-46. doi: 10.2217/nnm.10.90.
To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice.
MATERIALS & METHODS: PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice.
RESULTS & DISCUSSION: PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice.
PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.
研究作为抗癌药物顺铂药物递送载体的聚乙二醇（PEG）化单壁碳纳米管（SWCNT）在小鼠体内的分布和清除情况。
将 PEG 层附着在 SWCNT 上并分散在水介质中，使用动态光散射、扫描透射电子显微镜和拉曼光谱进行表征。体外使用 Annexin-V 测定法评估细胞毒性，并通过组织学染色和拉曼光谱研究小鼠中的分布和清除途径。研究了 PEG-SWCNT-顺铂对肿瘤生长抑制的疗效。
与对照组相比，PEG-SWCNT 在水介质中得到了有效分散，并且体外不会诱导细胞凋亡。静脉注射纳米管生物缀合物后，小鼠几种重要器官组织的苏木精和伊红染色和 SWCNT 的拉曼带表明，与 PEG-SWCNT 相比，对照 SWCNT 作为大聚集体在肺组织中沉积，而 PEG-SWCNT 则很少或没有聚集。粪便中特征性的 SWCNT 拉曼带表明存在胆汁或肾脏排泄途径。通过 Z 对比度扫描透射电子显微镜观察到生物缀合物上顺铂的附着。带有靶向配体 EGF 的 PEG-SWCNT-顺铂成功抑制了小鼠头颈部肿瘤异种移植的生长。
与对照 SWCNT 相比，PEG-SWCNT 形成了更高度分散的递送载体，当负载顺铂和 EGF 时，可抑制鳞状细胞瘤的生长。
