Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer.
Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer.
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DOI：
10.1016/j.jconrel.2015.01.026
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Lin W
中科院分区：
文献类型：
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作者：
Poon C;He C;Liu D;Lu K;Lin W
吉西他滨长期以来一直是治疗胰腺导管腺癌（PDAC）的标准治疗，尽管其药代动力学/动力学较差且耐药性迅速发展。在这项研究中，我们开发了一种基于纳米配位聚合物-1（NCP-1）的新型纳米颗粒平台，用于同时递送两种化疗药物奥沙利铂和吉西他滨单磷酸盐（GMP），浓度为30 wt.%。和12 wt.%药物负荷，分别。在体外观察到奥沙利铂和GMP对AsPc-1和BxPc-3胰腺癌细胞的强协同治疗作用。与单独携带奥沙利铂或GMP的NCP颗粒相比，NCP-1颗粒有效地避免了体内单核吞噬细胞系统（MPS）的摄取，血液循环半衰期长，为10.1±3.3 h，并有效抑制肿瘤生长。我们的研究结果表明，NCP-1是一种新型的纳米载体，用于共同递送两种化疗药物，这两种化疗药物具有独特的作用机制，可以同时破坏多种抗癌途径，具有最大的治疗效果和最小的副作用。
Gemcitabine has long been the standard of care for treating pancreatic ductal adenocarcinoma (PDAC), despite its poor pharmacokinetics/dynamics and rapid development of drug resistance. In this study, we have developed a novel nanoparticle platform based on nanoscale coordination polymer-1 (NCP-1) for simultaneous delivery of two chemotherapeutics, oxaliplatin and gemcitabine monophosphate (GMP), at 30 wt.% and 12 wt.% drug loadings, respectively. A strong synergistic therapeutic effect of oxaliplatin and GMP was observed in vitro against AsPc-1 and BxPc-3 pancreatic cancer cells. NCP-1 particles effectively avoid uptake by the mononuclear phagocyte system (MPS) in vivo with a long blood circulation half-life of 10.1±3.3 h, and potently inhibit tumor growth when compared to NCP particles carrying oxaliplatin or GMP alone. Our findings demonstrate NCP-1 as a novel nanocarrier for the co-delivery of two chemotherapeutics that have distinctive mechanisms of action to simultaneously disrupt multiple anticancer pathways with maximal therapeutic efficacy and minimal side effects.