Nanoscale coordination polymers for platinum-based anticancer drug delivery
Nanoscale coordination polymers for platinum-based anticancer drug delivery
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DOI：
10.1021/ja803383k
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发表时间：
2008-09-03
影响因子：
15
通讯作者：
Lin, Wenbin
中科院分区：
文献类型：
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作者：
Rieter, William J.;Pott, Kimberly M.;Lin, Wenbin
含铂纳米级配位聚合物（NCP）的分子式为Tb-2(DSCP)(3)(H2O)(12)（其中DSCP代表disuccinatocisplatin）， NCP-1，通过添加劣质溶剂从Tb3+离子和DSCP桥接配体的水溶液中析出。SEM和TEM图像显示，合成的NCP-1为球形结构，DLS直径为58.3 +/- 11.3 nm。NCP-1颗粒被包裹在非晶二氧化硅的外壳中，以防止在水中快速溶解。所得到的二氧化硅包覆颗粒NCP-1的DSCP释放半衰期明显延长（7 nm二氧化硅包覆的NCP-1'的半衰期约为9小时，而合成的NCP-1的半衰期约为1小时）。用人结肠癌细胞系（HT-29）进行的体外癌细胞细胞毒性实验表明，内化的NCP-1'颗粒容易释放DSCP片段，这些片段可能被还原为细胞毒性Pt(II)，从而使含Pt的ncp的抗癌效果优于顺铂标准。这种可降解纳米颗粒配方的通用性应该允许将ncp设计为各种生物和医学上重要的货物（如治疗剂和显像剂）的有效运载工具。
Pt-containing nanoscale coordination polymer (NCP) particles with the formula of Tb-2(DSCP)(3)(H2O)(12) (where DSCP represents disuccinatocisplatin), NCP-1, were precipitated from an aqueous solution of Tb3+ ions and DSCP bridging ligands via the addition of a poor solvent. SEM and TEM images showed that as-synthesized NCP-1 exhibited a spherical morphology with a DLS diameter of 58.3 +/- 11.3 nm. NCP-1 particles were stabilized against rapid dissolution in water by encapsulation in shells of amorphous silica. The resulting silica-coated particles NCP-1 exhibited significantly longer half-lives for DSCP release from the particles (a t(1/2) of similar to 9 h for NCP-1' with 7 nm silica coating vs t(1/2) of similar to 1 h for as-synthesized NCP-1). In vitro cancer cell cytotoxicity assays with the human colon carcinoma cell line (HT-29) showed that internalized NCP-1' particles readily released the DSCP moieties which were presumably reduced to cytotoxic Pt(II) species to give the Pt-containing NCPs anticancer efficacy superior to the cisplatin standard. The generality of this degradable nanoparticle formulation should allow for the design of NCPs as effective delivery vehicles for a variety of biologically and medically important cargoes such as therapeutic and imaging agents.