In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases

Go Oshima, Nining Guo, Chunbai He, Melinda E. Stack, Christopher Poon, Abhineet Uppal, Sean C. Wightman, Akash Parekh, Kinga B. Skowron, Mitchell C. Posner, Wenbin Lin, Nikolai N. Khodarev, Ralph R. Weichselbaum

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1588-1595
ページ数8
ジャーナルMolecular Therapy
25
7
DOI
出版ステータスPublished - 2017 7 5

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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