Despite significant advances, the
radiotherapy and
chemotherapy protocols marginally improve the overall survival of patients with
glioblastoma.
Lipoplatin(TM), and Lipoxal(TM), the liposomal formulations of
cisplatin and
oxaliplatin respectively, were tested on the F98
glioma cells for their ability to improve the cell uptake and increase the synergic effect when combined with ionizing radiation. The cytotoxicity and synergic effect of
platinum compounds were assessed by colony formation assay, while the cellular uptake was measured by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with
platinum compounds, cells were irradiated (1.5-6.6 Gy) with a (60)Co source. The liposomal formulations were compared to their
liposome-free analogs and to
carboplatin. The concomitant treatment of F98 cells with
carboplatin and radiation produced the highest
radiosensitizing effect (30-fold increase). Among the
platinum compounds tested,
Lipoplatin(TM) produced the most promising results. This liposomal formulation of
cisplatin improved the cell uptake by 3-fold, and its radiosensitizing potential was enhanced by 14-fold. Although Lipoxal(TM) can potentially reduce the adverse effect of
oxaliplatin, a synergic effect with radiation was measured only when incubated at a concentration higher than its IC50. Conversely, concomitant treatment with
cisplatin did not result in a synergic effect, as in fact a radioprotective effect was measured on the F98 cells. In conclusion, among the five
platinum compounds tested,
carboplatin and
Lipoplatin(TM) showed the best
radiosensitizing effect.
Lipoplatin(TM) seems the most promising since it led to the best cellular incorporation and has already been reported to be less neurotoxic than other
platinum compounds.