Development of a novel orthotopic non-small cell lung cancer model and therapeutic benefit of 2'-(2-bromohexadecanoyl)-docetaxel conjugate nanoparticles.
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.
Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lei
L
Peng
Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lan
L
Feng
Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hong
H
Yuan
Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
S Rahima
SR
Benhabbour
Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: mumper@email.unc.edu.
Russell J
RJ
Mumper
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging; D053758:Nanoparticles; D049268:Positron-Emission Tomography; D043823:Taxoids / Q000737:chemistry / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
D043823:Taxoids; D000077143:Docetaxel
Bioluminescence; Docetaxel conjugate; Lipid nanoparticles; Micro PET/CT; Orthotopic lung cancer model