Poon Christopher, He Chunbai, Liu Demin, Lu Kuangda, Lin Wenbin
Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA.
Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA.
J Control Release. 2015 Mar 10;201:90-9. doi: 10.1016/j.jconrel.2015.01.026. Epub 2015 Jan 22.
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 ± 3.3h, 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.
尽管吉西他滨的药代动力学/药效学较差且耐药性发展迅速，但长期以来它一直是治疗胰腺导管腺癌（PDAC）的标准疗法。在本研究中，我们基于纳米级配位聚合物-1（NCP-1）开发了一种新型纳米颗粒平台，用于同时递送两种化疗药物，分别为奥沙利铂和单磷酸吉西他滨（GMP），药物负载量分别为30 wt.%和12 wt.%。在体外对AsPc-1和BxPc-3胰腺癌细胞观察到奥沙利铂和GMP具有强大的协同治疗效果。NCP-1颗粒在体内能有效避免被单核吞噬细胞系统（MPS）摄取，血液循环半衰期长达10.1±3.3小时，与单独携带奥沙利铂或GMP的NCP颗粒相比，能有效抑制肿瘤生长。我们的研究结果表明，NCP-1作为一种新型纳米载体，可共同递送两种作用机制不同的化疗药物，以同时破坏多个抗癌途径，实现最大治疗效果和最小副作用。
