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

Abstract

e13546 Background: A key research objective in radiation oncology is to identify agents that can improve chemoradiotherapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiotherapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiotherapy, 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 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 vivousing mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared to that of after Taxol administration. Results: Genexol-PM have 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 excellent radiosensitizer and is more effective than Taxol, its small molecule counterpart at the half maximal inhibitory concentration (IC50). In vivostudy 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 and liver tissue than Taxol at 6 hours post administration. 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 chemoradiotherapy for NSCLC.