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Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy

机译:具有触发释放特性的自组装纳米级配位聚合物可用于有效的抗癌治疗

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摘要

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 tumor xenograft models evaluated, including CT26 colon cancer, H460 lung cancer, and AsPC-1 pancreatic cancer, pegylated NCPs show superior potency and efficacy compared to free drugs. As the first example of using NCPs as nanotherapeutics with enhanced antitumor activities, this study establishes NCPs as a promising drug delivery platform for cancer therapy.
机译:纳米级配位聚合物(NCP)是由金属离子和有机桥联配体自组装而成的,凭借可调整的组成,尺寸和形状,可以克服现有药物输送系统的许多缺点;高药物负荷;易于表面改性;和固有的生物降解性。在这里,我们报告了携带48±3 wt%的顺铂前药和45±5 wt%的奥沙利铂前药的双膦酸锌NCP的自组装。在小鼠体内的体内药代动力学研究表明,单核吞噬细胞系统对聚乙二醇化NCP的吸收最少,对于携带顺铂和奥沙利铂的NCP,其血液循环半衰期分别为16.4±2.9和12.0±3.9 h。在评估的所有肿瘤异种移植模型中,包括CT26结肠癌,H460肺癌和AsPC-1胰腺癌,与游离药物相比,聚乙二醇化NCP显示出更强的效力和功效。作为使用NCPs作为具有增强的抗肿瘤活性的纳米治疗药物的第一个例子,本研究建立了NCPs作为有希望的癌症治疗药物递送平台。

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