Local Delivery of Ferrociphenol Lipid Nanocapsules Followed by External Radiotherapy as a Synergistic Treatment Against Intracranial 9L Glioma Xenograft
The goal of the present study was to evaluate the efficacy of a new organometallic drug, ferrociphenol (Fc-diOH), in combination with external radiotherapy in intracerebral 9L glioma model. We tested the hypothesis that the combination of external radiotherapy with Fc-diOH could potentiate the action of this drug.
9L cells were treated with Fc-diOH-LNCs (from 0.01 to 1 µmol/L) and irradiated with external radiotherapy (from 2 to 40 Gy). In vivo assessment was evaluated by the inoculation of 9L cells in Fisher rats. Chemotherapy with Fc-diOH-LNCs (0.36 mg/rat) was administered by means of convection-enhanced delivery (CED), and the treatment was followed by three irradiations of 6 Gy doses (total dose = 18 Gy).
In vitro evaluations evidenced that a combined treatment with Fc-diOH-LNCs and irradiations showed synergistic antitumor activity on 9L cells. Combining cerebral irradiation with CED of Fc-diOH-LNCs led to a significantly longer survival and the existence of long-term survivors compared to Fc-diOH-LNCs-treated animals (p < 0.0001) and to the group treated with blank LNCs + radiotherapy (p = 0.0079).
The synergistic effect between ferrociphenol-loaded LNCs and radiotherapy was due to a closely oxidative relationship. Upon these considerations, Fc-diOH-LNCs appear to be an efficient radiosensitive anticancer drug delivery system.
Key Wordsconvection-enhanced delivery glioma iron lipid nanocapsules radiotherapy
The authors would like to thank Emilien Porcher, N. Trinh Huynh (Inserm U646, Angers, France), and Pierre Legras (Service Commun d’Animalerie Hospitalo-Universitaire, Angers, France) for skillful technical support with animals, and Elisabeth Hillard for English corrections. This work was supported by a “Région des Pays de la Loire” grant, by the “Cancéropôle Grand Ouest” and by “La Ligue Nationale Contre le Cancer” (équipe labellisée 2007).
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