Feazell Rodney P, Nakayama-Ratchford Nozomi, Dai Hongjie, Lippard Stephen J
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Am Chem Soc. 2007 Jul 11;129(27):8438-9. doi: 10.1021/ja073231f. Epub 2007 Jun 15.
Amine functionalized soluble single walled carbon nanotubes (SWNTs) were derivatized with cisplatin prodrug conjugates as a delivery system by which to internalize multiple prodrug centers. The platinum(IV) complex, ,,-[Pt(NH)Cl(OEt)(OCCHCHCOH)], was tethered to the surface of the carbon nanotubes through peptide linkages formed by the reaction of the SWNT-tethered amines with the carboxylate moiety. The SWNTs are taken into testicular cancer cells by endocytosis where the drop in pH facilitates reductive release of the platinum(II) core complex, which then readily diffuses throughout the cell, as determined by platinum atomic absorption spectroscopy. The entrapment of the SWNTs within the endosomes was confirmed by fluorescence microscopy of SWNTs containing both tethered fluorescein and platinum units. The cytotoxicity of the free platinum(IV) complex increases by greater than 100-fold when attached to the surface of the functionalized SWNTs.
胺功能化的可溶性单壁碳纳米管（SWNTs）用顺铂前药共轭物进行衍生化，作为一种递送系统，通过该系统可内化多个前药中心。铂（IV）配合物，，，-[Pt(NH)Cl(OEt)(OCCHCHCOH)]，通过SWNT连接的胺与羧酸盐部分反应形成的肽键连接到碳纳米管表面。SWNTs通过内吞作用进入睾丸癌细胞，在细胞内pH值下降促进铂（II）核心配合物的还原释放，然后通过铂原子吸收光谱法测定，该配合物随后很容易在整个细胞中扩散。通过对同时含有连接的荧光素和铂单元的SWNTs进行荧光显微镜观察，证实了SWNTs被包裹在内体中。当附着在功能化SWNTs表面时，游离铂（IV）配合物的细胞毒性增加超过100倍。
