Combination of microRNA therapeutics with small-molecule anticancer drugs: mechanism of action and co-delivery nanocarriers

Adv Drug Deliv Rev. 2015 Jan:81:184-97. doi: 10.1016/j.addr.2014.09.010. Epub 2014 Oct 2.

Abstract

MicroRNAs (miRNAs) regulate multiple molecular pathways vital for the hallmarks of cancer with a high degree of biochemical specificity and potency. By restoring tumor suppressive miRNAs or ablating oncomiRs, miRNA-based therapies can sensitize cancer cells to conventional cytotoxins and the molecularly targeted drugs by promoting apoptosis and autophagy, reverting epithelial-to-mesenchymal transition, suppressing tumor angiogenesis, and downregulating efflux transporters. The development of miRNA-based therapeutics in combination with small-molecule anticancer drugs provides an unprecedented opportunity to counteract chemoresistance and improve treatment outcome in a broad range of human cancers. This review summarizes the mechanisms and advantages for the combination therapies involving miRNAs and small-molecule drugs, as well as the recent advances in the co-delivery nanocarriers for these agents.

Keywords: Anti-miR; Co-delivery; Combination therapy; MicroRNA mimic; Nanocarrier; Small-molecule anticancer drug.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm
  • Humans
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • Molecular Targeted Therapy
  • Nanostructures
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • MicroRNAs