Liu Demin, Poon Christopher, Lu Kuangda, He Chunbai, Lin Wenbin
Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Nat Commun. 2014 Jun 25;5:4182. doi: 10.1038/ncomms5182.
Nanoscale coordination polymers (NCPs) are self-assembled from metal ions and organic bridging ligands, and can overcome many drawbacks of existing drug delivery systems by virtue of tunable compositions, sizes and shapes, high drug loadings, ease of surface modification and intrinsic biodegradability. Here we report the self-assembly of zinc bisphosphonate NCPs that carry 48 ± 3 wt% cisplatin prodrug and 45 ± 5 wt% oxaliplatin prodrug. In vivo pharmacokinetic studies in mice show minimal uptake of pegylated NCPs by the mononuclear phagocyte system and excellent blood circulation half-lives of 16.4 ± 2.9 and 12.0 ± 3.9 h for the NCPs carrying cisplatin and oxaliplatin, respectively. In all tumour xenograft models evaluated, including CT26 colon cancer, H460 lung cancer and AsPC-1 pancreatic cancer, pegylated NCPs show superior potency and efficacy compared with free drugs. As the first example of using NCPs as nanotherapeutics with enhanced antitumour activities, this study establishes NCPs as a promising drug delivery platform for cancer therapy.
纳米级配位聚合物(NCPs)由金属离子和有机桥联配体自组装而成,凭借其可调节的组成、尺寸和形状、高载药量、易于表面修饰以及固有的生物降解性,能够克服现有药物递送系统的诸多缺点。在此,我们报道了携带48±3 wt%顺铂前药和45±5 wt%奥沙利铂前药的双膦酸锌NCPs的自组装。在小鼠体内进行的药代动力学研究表明,聚乙二醇化NCPs被单核吞噬细胞系统摄取的量极少,携带顺铂和奥沙利铂的NCPs在血液循环中的半衰期分别长达16.4±2.9小时和12.0±3.9小时。在所有评估的肿瘤异种移植模型中,包括CT26结肠癌、H460肺癌和AsPC-1胰腺癌,聚乙二醇化NCPs与游离药物相比显示出更强的效力和疗效。作为将NCPs用作具有增强抗肿瘤活性的纳米治疗药物的首个实例,本研究确立了NCPs作为一种有前景的癌症治疗药物递送平台的地位。