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 AlPcS2a- based PCI of
bleomycin was compared to: (1) AlPcS2a-PDT, and (2) bleomycin. In all cases, monolayers and spheroids
were incubated in AlPcS2a (18 h), bleomycin (4 h), or AlPcS2a (18 h) + bleomycin (4 h) and were
subsequently exposed to 670 nm light. Toxicity was evaluated using colony formation assays or spheroid
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) AlPcS2a -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 AlPcS2a-mediated PCI
can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.