Preclinical evaluation of genexol-pm, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer

Michael E. Werner, Natalie D. Cummings, Manish Sethi, Edina C. Wang, Rohit Sukumar, Dominic T. Moore, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Genexol-PM was evaluated preclinically as a radiosensitizer for chemoradiation therapy of non-small cell lung cancer (NSCLC). Using NSCLC cell lines and mouse xenograft models of NSCLC, we demonstrated that Genexol-PM is an effective radiosensitizer and is more effective than Taxol. We also found that Genexol-PM leads to lower paclitaxel dose in normal lung when compared with Taxol. Our findings support the clinical evaluation Purpose: Akey 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 and Materials: 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-PMadministration were quantified and compared with that after Taxol administration. Results: Genexol-PMhas a size of 23.91± 0.41nmand surface charge of-8.1± 3.1mV. 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-PMas 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.

Original languageEnglish (US)
Pages (from-to)463-468
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume86
Issue number3
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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