Oshima Go, Guo Nining, He Chunbai, Stack Melinda E, Poon Christopher, Uppal Abhineet, Wightman Sean C, Parekh Akash, Skowron Kinga B, Posner Mitchell C, Lin Wenbin, Khodarev Nikolai N, Weichselbaum Ralph R
Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA; Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Mol Ther. 2017 Jul 5;25(7):1588-1595. doi: 10.1016/j.ymthe.2017.04.005. Epub 2017 Apr 28.
Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs.
通常联合使用多种治疗药物来有效控制转移性肿瘤。最近，我们描述了与寡转移状态相关的 microRNA，在这种状态下，有限数量的转移性肿瘤会进展为更有利的结果。在此，我们报告了使用纳米级配位聚合物（NCPs）将寡转移 microRNA（miR-655-3p）有效递送至结直肠癌肝转移灶。NCPs 显示出 microRNA 在转移性肝肿瘤中的靶向性和延长分布。肿瘤靶向 microRNA miR-655-3p 与奥沙利铂共同递送时可抑制肿瘤生长，表明 microRNA 与铂类药物之间存在相加或协同相互作用。这是系统性给药纳米颗粒将寡转移 microRNA 递送至晚期转移性肝肿瘤并显示出肿瘤抑制作用的首个已知实例。我们的结果提示了一种通过使用肿瘤特异性 NCPs 共同递送 microRNA 和传统细胞毒性药物来治疗转移性肝病的潜在策略。
