Photochemical delivery of bleomycin in malignant glioma cells

Abstract

Photochemical Delivery of Bleomycin in Malignant Glioma Cells by Joseph William Blickenstaff III Dr. Steen Madsen, Examination Committee Chair Professor of Health Physics University of Nevada, Las Vegas Despite continued efforts, glioblastoma multiforme (GBM) remains an incurable form of primary brain cancer. Surgical resection followed by radiation treatment and chemotherapy have been the most effective modalities in prolonging median survival time to 14 months. This research aims to study the response of two different cell culture models to a novel drug delivery method termed photochemical internalization (PCI). PCI is a technique to improve the utilization of macromolecules (e.g. the chemotherapeutic drug bleomycin) in site-specific cancer therapy. This concept is based on the use of specially designed photosensitizers (e.g. aluminum phthalocyanine disulfonate; AlPcS2a) which preferentially localize in the membranes of endocytic vesicles. The utility of PCI for treating malignant gliomas was investigated in vitro using: (1) F98 rat glioma monolayer cells, and (2) biopsy-derived human glioma spheroids. For both in vitro systems, PCI was found to interact in a synergistic manner resulting in significant toxicity. For example, the combination of 1.5 J/cm photodynamic therapy (PDT) and 0.25 (xg/mL bleomycin resulted in approximately 25% survival in F98 rat glioma cells while only 35% of human glioma spheroids were observed to be growing iii two weeks post treatment. Overall, the degree of synergism was found to be less pronounced in the spheroid model. Collectively, the results show that AlPcS2a-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.