title: Differential cell responses to nanoparticle docetaxel and small molecule docetaxel at a sub-therapeutic dose range.
abstract: Current preclinical evaluations of nanoparticle taxanes have focused on the effect of nanoparticle size and shape on the efficacy and toxicity. It is generally assumed that nanoparticle therapeutics have the same cellular response on tumor and normal cells as their small molecule counterparts. Here, we show that nanoparticle taxanes can mediate cellular effects distinct from that of small molecule taxanes at the sub-therapeutic dose range. Cells that are exposed to two polymeric nanoparticle formulations of docetaxel were found to undergo a different cell cycle and cell fate than those of cells that were exposed to small molecule docetaxel. Our results suggest that nanoparticle formulation of therapeutics can affect the therapeutic effect of its cargo.
  
  
  BACKGROUND
  This study investigates the differences between subtherapeutic doses of docetaxel applied as small molecules vs. nanoparticle formulations, demonstrating differential effects on the cell cycle and overall cell fate. The study suggests that the carrier may change the therapeutic effects of its cargo, which has important implications on future research.
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Edina C
authors.initials: EC
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sinnott
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Werner
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Sethi
authors.affiliation: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Angelique W
authors.initials: AW
authors.lastname: Whitehurst
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: zawang@med.unc.edu.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D008823:Micelles; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D043823:Taxoids; D049452:Green Fluorescent Proteins; D000077143:Docetaxel
keywords: Controlled drug release; Cytotoxicity; Drug delivery; Nanomedicine; Nanoparticle
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