title: Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer.
abstract: OBJECTIVE
  A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease.
  
  
  METHODS
  The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration.
  
  
  RESULTS
  Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration.
  
  
  CONCLUSIONS
  We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.|Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
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-Chapel Hill, Chapel Hill, North Carolina.|Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Cummings
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.|Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Manish
authors.initials: M
authors.lastname: Sethi
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.|Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Edina C
authors.initials: EC
authors.lastname: Wang
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.|Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sukumar
authors.affiliation: Division of Biostatistics and Data Management, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.|Division of Biostatistics and Data Management, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000627:therapeutic use*; D017239:Paclitaxel / Q000627:therapeutic use*; D011108:Polymers / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel