Photochemical internalization enhances the efficacy of bleomycin in malignant glioma cells

Abstract

The utility of photochemical internalization (PCI) for the treatment of malignant gliomas was investigated in vitro using: (1) monolayers consisting of F98 rat glioma cells, and (2) human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of AlPcS_2a- based PCI of bleomycin was compared to: (1) AlPcS_2a-PDT, and (2) bleomycin. In all cases, monolayers and spheroids were incubated in AlPcS_2a (18 h), bleomycin (4 h), or AlPcS_2a (18 h) + bleomycin (4 h) and were subsequently exposed to 670 nm light. Toxicity was evaluated using colony formation assays or spheroid growth kinetics. Neither F98 rat glioma cells in monolayer nor human glioma spheroids were found to be particularly sensitive to the effects of low irradiance (5 mW cm^-2), low radiant exposure (1.5 J cm^-2) AlPcS_2a -PDT. Bleomycin was found to be moderately toxic to F98 cells in monolayer at relatively low concentrations - incubation of F98 cells in 0.1 μg ml^-1 for 4 hours resulted in 80% survival. Under similar incubation conditions, the effects of bleomycin on human glioma spheroids were negligible. In both in vitro systems investigated, the PCI effect was found to be significant. For example, PCI consisting of a radiant exposure of 1.5 J cm^-2 together with 0.25 μg ml^-1 bleomycin resulted in approximately 20 and 65 % survival of F98 rat glioma cells and human glioma spheroids respectively. These results show that AlPcS_2a-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.