Development of a novel orthotopic non-small cell lung cancer model and therapeutic benefit of 2'-(2-bromohexadecanoyl)-docetaxel conjugate nanoparticles

Nanomedicine. 2014 Oct;10(7):1497-506. doi: 10.1016/j.nano.2014.03.016. Epub 2014 Apr 4.

Abstract

The aims of these studies were to establish an orthotopic non-small-cell lung cancer (NSCLC) mouse model and to investigate the therapeutic efficacy of lipid-based nanoparticles (NPs) containing 2'-(2-bromohexadecanoyl)-docetaxel (Br-C16-DX) in this new model. A novel orthotopic NSCLC model was established in nude mice through a dorsal side injection of luciferase-expressing A549 cells. The model was characterized by a survival study, histological staining, bioluminescence imaging and PET/CT imaging. The therapeutic efficacy of the Br-C16-DX NPs versus Taxotere® was investigated in this model. The results demonstrated that mouse survival time was significantly prolonged by weekly intravenous administration of the NPs or Taxotere. Furthermore, the NP group had 35 days longer progression-free survival and 27 days longer median survival compared to the Taxotere group. It was concluded that the developed orthotopic NSCLC model represents a feasible, reproducible, and clinically relevant experimental mouse model to test current and potential therapies including nanomedicines. From the clinical editor: This team of authors has developed an orthotopic non-small cell lung cancer model, and demonstrates that it represents a feasible, reproducible, and clinically relevant experimental mouse model to test current and potential therapies including nanomedicines.

Keywords: Bioluminescence; Docetaxel conjugate; Lipid nanoparticles; Micro PET/CT; Orthotopic lung cancer model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Docetaxel
  • Female
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Multimodal Imaging
  • Nanoparticles*
  • Positron-Emission Tomography
  • Taxoids / chemistry
  • Taxoids / therapeutic use*
  • Tomography, X-Ray Computed

Substances

  • Taxoids
  • Docetaxel