title: Photochemical internalization of bleomycin for glioma treatment.
abstract: 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.
authors.affiliation: University of California, Department of Neurosurgery, Irvine, Orange, CA 92801, USA. marlonmathews@yahoo.com
authors.forename: Marlon S
authors.initials: MS
authors.lastname: Mathews
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Blickenstaff
authors.forename: En-Chung
authors.initials: EC
authors.lastname: Shih
authors.forename: Genesis
authors.initials: G
authors.lastname: Zamora
authors.forename: Van
authors.initials: V
authors.lastname: Vo
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Sun
authors.forename: Henry
authors.initials: H
authors.lastname: Hirschberg
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Madsen
mesh_terms: D001761:Bleomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*
chemical_list: D001761:Bleomycin