Acid-sensitive lipidated doxorubicin prodrug entrapped in nanoemulsion impairs lung tumor metastasis in a breast cancer model

Nanomedicine (Lond). 2017 Aug;12(15):1751-1765. doi: 10.2217/nnm-2017-0091. Epub 2017 Jul 13.

Abstract

Aim: To develop an acid-sensitive lipidated, doxorubicin (Dox) prodrug (C16-Dox) to be entrapped in lipid nanoemulsion (NE-C16-Dox) as a nanocarrier to treat breast cancer models (in vitro and in vivo).

Results: We report the efficacy of NE-C16-Dox in in vitro experiments, as well as the improved chemotherapeutic index and tumor-control efficacy compared with treatment with free Dox in an in vivo murine 4T1 breast cancer model. In addition, NE-C16-Dox allowed the use of a higher dose of Dox, acceptable biocompatibility and a significant reduction in lung metastasis.

Conclusion: Taken together, these results indicate that NE-C16-Dox is promising for breast cancer treatment, thus creating possibilities to translate these nanotechnology concepts to clinical applications.

Keywords: breast cancer; doxorubicin; drug delivery; metastasis; nanoemulsion; pH-sensitive.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers
  • Drug Liberation
  • Emulsions
  • Female
  • Humans
  • Lipids / chemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Neoplasm Metastasis
  • Particle Size
  • Prodrugs / chemical synthesis
  • Prodrugs / pharmacology*
  • Surface Properties

Substances

  • Drug Carriers
  • Emulsions
  • Lipids
  • Prodrugs
  • Doxorubicin