Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Abstract

Despite significant advances, the radiotherapy and chemotherapy protocols marginally improve the overall survival of patients with glioblastoma. Lipoplatin ™ , and Lipoxal ™ , 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 to 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 ™ 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 ™ 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 ™ showed the best radiosensitizing effect. Lipoplatin ™ 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.

Increased radiosensitivity of colorectal tumors with intra-tumoral injection of low dose of gold nanoparticles

“…Then, the cells were digested in 2 mL of 30% hydrogen peroxide and 2 mL of 70% nitric acid, and the concentration of gold was determined by ICP-MS analysis. 29 subcellular localization of Tio-gNPs HCT116 cells were incubated with 0.25 mg/mL of Tio-GNPs for 24 hours, and then rinsed with 0.1 M phosphate buffer, fixed with ice-cold 2% paraformaldehyde for 20 minutes, and washed twice with 0.1 M phosphate buffer. The samples were kept in 0.2 M citrate buffer, pH 7.4.…”

Uptake and intracellular release kinetics of liposome formulations in glioma cells

“…A significant difference in PI fluorescence levels between formulation D and E was observed at 12 (p < 0.001) and 24 h (p < 0.001) in F98 cells, with a higher PI signal maintained in formulation E. Although this unexpected result deserves further investigation, we hypothesize that, owing to its higher PEG-lipid content, formulation E might simply better resist cellular degradation than D over time, thus allowing less PI elimination at 12 and 24 h in both cell lines. Inhibitory effect of PEG-modified lipids on cellular uptake of liposomes and especially on intracellular release of their content might explain why the free antineoplastic drugs yield higher cytoxicity than pegylated liposomal forms in studies comparing the efficiency of different formulations (Sharma et al, 1997;Kobayashi et al, 2007;Charest et al, 2009).…”

Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones

“…It has been proposed that the ability of liposomes to bypass the P-glycoprotein pumps responsible for multidrug resistance can promote a higher uptake of chemotherapeutic agents in resistant cancer cells. Furthermore, among platinum compounds and their liposomal form tested in this study, carboplatin and carboplatin-loaded liposomes yield the best radiosensitizing effects even at low concentrations, showing the best cellular incorporation, and have already been reported to be less neurotoxic than other platinum compounds [169]. Other study showed that cisplatin-loaded polybutyl cyanoacrylate nanoparticles enhanced mean survival time and reduced side effects [170] ( Table 2).…”

“…To prevent the side effects caused by platinum compounds, a potential approach consists of incorporating the platinum agent into liposomes and combining this with irradiation to obtain a synergistic effect. There is an important increase in cell uptake when drugs are loaded in liposomes [169] (Table 2). It has been proposed that the ability of liposomes to bypass the P-glycoprotein pumps responsible for multidrug resistance can promote a higher uptake of chemotherapeutic agents in resistant cancer cells.…”