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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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. Oshima et al. describe nanoscale coordination polymers (NCPs) with oxaliplatin and metastases-suppressive miR-655-3p detected in oligometastatic patients. Designed NCPs suppressed colorectal liver metastases in preclinical models. Results suggest a therapeutic strategy for metastatic liver disease by the co-delivery of oligometastatic microRNAs and conventional drugs using tumor-specific NCPs.

Original languageEnglish
JournalMolecular Therapy
DOIs
Publication statusAccepted/In press - 2017 Feb 6
Externally publishedYes

Keywords

  • Colorectal cancer
  • Liver
  • Metastases
  • MicroRNA
  • Nanoparticles

ASJC Scopus subject areas

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

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  • Cite this

    Oshima, G., Guo, N., He, C., Stack, M. E., Poon, C., Uppal, A., Wightman, S. C., Parekh, A., Skowron, K. B., Posner, M. C., Lin, W., Khodarev, N. N., & Weichselbaum, R. R. (Accepted/In press). In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2017.04.005