Photochemical internalization of bleomycin for glioma treatment.

Publication Type:

Journal Article


Journal of biomedical optics, Volume 17, Issue 5, p.058001 (2012)


We study the use of photochemical internalization (PCI) for enhancing chemotherapeutic response to malignant glioma cells in vitro. Two models are studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared to AlPcS(2a)-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS(2a) (PDT effect), bleomycin (chemotherapy effect), or AlPcS(2a)+bleomycin (PCI effect) and were illuminated (670 nm). Toxicity was evaluated using colony formation assays or spheroid growth kinetics. F98 cells in monolayer/spheroids were not particularly sensitive to the effects of low radiant exposure (1.5  J/cm(2) @ 5  mW/cm(2)) AlPcS(2a)-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations-incubation of F98 cells in 0.1  μg/ml for 4 h resulted in 80% survival, but less toxic in human glioma spheroids respectively. In both in vitro systems investigated, a significant PCI effect is seen. PCI using 1.5  J/cm(2) together with 0.25  μg/ml bleomycin resulted in approximately 20% and 18% 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.