electron paramagnetic resonance highlights that the oxygen effect contributes to the radiosensitizing effect of paclitaxel电子顺磁共振强调了紫杉醇的氧效应有助于机体效应.pdfVIP

Electron Paramagnetic Resonance Highlights That the Oxygen Effect Contributes to the Radiosensitizing Effect of Paclitaxel 1. 2. 1 ´ 2 1 Fabienne Danhier , Pierre Danhier , Nicolas Magotteaux , Geraldine De Preter , Bernard Ucakar , 2 ´ ´ 2 2 ´ ´ 1 Oussama Karroum , Benedicte Jordan , Bernard Gallez , Veronique Preat * ´ 1 Pharmaceutics and Drug Delivery, Louvain Drug Research Institute, Universite Catholique de Louvain, Brussels, Belgium, 2 Laboratory of Biomedical Magnetic ´ Resonance, Louvain Drug Research Institute, Universite Catholique de Louvain, Brussels, Belgium Abstract Background: Paclitaxel (PTX) is a potent anti-cancer chemotherapeutic agent and is widely used in the treatments of solid tumors, particularly of the breast and ovaries. An effective and safe micellar formulation of PTX was used to administer higher doses of PTX than TaxolH (the current commercialized drug). We hypothesize that PTX-loaded micelles (M-PTX) may enhance tumor radiosensitivity by increasing the tumor oxygenation (pO2). Our goals were (i) to evaluate the contribution of the ‘‘oxygen effect’’ to the radiosensitizing effect of PTX; (ii) to demonstrate the therapeutic relevance of the combination of M-PTX and irradiation and (iii) to investigate the underlying mechanisms of the observed oxygen effect. Methodology and Principal Findings: We used (PEG-p-(CL-co-TMC)) polymeric micelles to solubilize PTX. pO2 was measured on