Dispersion of cisplatin-loaded carbon nanohorns with a conjugate comprised of an artificial peptide aptamer and polyethylene glycol
Dispersion of cisplatin-loaded carbon nanohorns with a conjugate comprised of an artificial peptide aptamer and polyethylene glycol
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DOI：
10.1021/mp070022t
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发表时间：
2007-09-01
影响因子：
4.9
通讯作者：
Shiba, Kiyotaka
中科院分区：
文献类型：
--
作者：
Matsumura, Sachiko;Ajima, Kumiko;Shiba, Kiyotaka
将疏水性单壁碳纳米角(SWNH)通过聚乙二醇(PEG)和多肽适配子(NHBP-1)组成的共轭分子进行非共价修饰，将其分散在水介质中。将平均相对分子质量分别为20000和5000的聚乙二醇偶联物与NHBP-1的N-末端偶联，分别得到20PEGNHBP和5PEGNHBP。与20PEGNHBP或5PEGNHBP混合的氧化SWNHs(OxSWNHs)在水中分散良好，并通过凝胶过滤柱，而经聚乙二醇化的oxSWNHs粘在柱子的顶部。尽管介质中盐的存在显著降低了oxSWNHs的分散性，但oxSWNHs/20PEGNHBP复合体在磷酸盐缓冲盐水(PBS)和细胞培养基中都能很好地分散。20PEGNHBP与oxSWNHs的结合量为0.32g/g oxSWNHs，动态光散射分析表明oxSWNHs/20PEGNHBP复合体的直径约为210 nm。结果表明，将化疗药物顺铂(CDDP)负载到oxSWNHs中的CDDP@oxSWNHs/20PEGNHBP在PBS和培养基中均能很好地分散，对癌细胞有很强的杀伤作用。载药碳纳米材料的良好分散性是此类材料临床应用的先决条件。
Hydrophobic single-wall carbon nanohorns (SWNHs) were dispersed in aqueous media by noncovalently modifying their surfaces with conjugate molecules comprised of polyethylene glycol (PEG) and a peptide aptamer (NHBP-1) that specifically bind to the surfaces of the SWNHs. The conjugates were synthesized by coupling PEG (average molecular weights of 20,000 and 5000) to the N-terminus of NHBP-1 to produce 20PEG-NHBP and 5PEG-NHBP, respectively. Oxidized SWNHs (oxSWNHs) mixed with 20PEG-NHBP or 5PEG-NHBP were well dispersed in water and passed through a gel filtration column, whereas the oxSWNHs treated with PEG stuck to the top of the column. Although the presence of salts in the media significantly impaired the dispersibility of the oxSWNHs, the oxSWNHs/20PEG-NHBP complexes were well dispersed in both the phosphate-buffered saline (PBS) and cell culture medium. The amount of 20PEG-NHBP bound to the oxSWNHs was estimated to be 0.32 g/g of oxSWNHs, and a dynamic light scattering analysis revealed the diameter of the oxSWNHs/20PEG-NHBP complex to be approximately 210 nm. We then showed that CDDP@oxSWNHs/20PEG-NHBP, in which the cancer chemotherapy drug cisplatin (CDDP) was loaded inside the oxSWNHs, was well dispersed in both the PBS and culture medium and exerted a potent cytotoxic effect against cancer cells. The good dispersion of drug-loaded carbon nanomaterials, like that seen here, is a prerequisite for the clinical application of such materials.