Soluble single-walled carbon nanotubes as longboat delivery systems for Platinum(IV) anticancer drug design
Soluble single-walled carbon nanotubes as longboat delivery systems for Platinum(IV) anticancer drug design
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DOI：
10.1021/ja073231f
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发表时间：
2007-07-11
影响因子：
15
通讯作者：
Lippard, Stephen J.
中科院分区：
文献类型：
--
作者：
Feazell, Rodney P.;Nakayama-Ratchford, Nozomi;Lippard, Stephen J.
以顺铂前药结合物为载体，将胺功能化的可溶单壁碳纳米管(SWNTs)内化为多个前药中心。铂(IV)络合物c，c，t-[Pt(NH3)(2)Cl2(OEt)(O2CCH2CH2CO2H)]通过单壁碳纳米管与羧酸基团反应形成的多肽键连接到碳纳米管表面。单壁碳纳米管通过内吞作用进入睾丸癌细胞，其中pH的下降促进了铂(II)核心络合物的还原释放，然后根据铂原子吸收光谱的测定，该络合物很容易扩散到整个细胞。同时含有荧光素和铂单元的单壁碳纳米管的荧光显微镜证实了单壁碳纳米管在内体中的包埋。当游离铂(IV)络合物附着在功能化的单壁碳纳米管表面时，其细胞毒性增加100倍。
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, c,c,t-[Pt(NH3)(2)Cl-2(OEt)(O2CCH2CH2CO2H)], 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 were 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 > 100-fold when the complex is attached to the surface of the functionalized SWNTs.