Research Papers: Therapeutic

Photochemical internalization of bleomycin for glioma treatment

[+] Author Affiliations
Marlon S. Mathews

University of California, Department of Neurosurgery, Irvine, 101 The City Drive South, Orange, California 92801

University of California, Beckman Laser Institute, Irvine, 1002 Health Sciences Road East, Irvine, California 92612

Joseph W. Blickenstaff, Van Vo, Steen J. Madsen

University of Nevada, Department of Health Physics and Diagnostic Sciences, Las Vegas, 4505 Maryland Parkway, Box 453037, Las Vegas, Nevada 89154

En-Chung Shih, Genesis Zamora, Chung-Ho Sun

University of California, Beckman Laser Institute, Irvine, 1002 Health Sciences Road East, Irvine, California 92612

Henry Hirschberg

University of California, Beckman Laser Institute, Irvine, 1002 Health Sciences Road East, Irvine, California 92612

University of Nevada, Department of Health Physics and Diagnostic Sciences, Las Vegas, 4505 Maryland Parkway, Box 453037, Las Vegas, Nevada 89154

J. Biomed. Opt. 17(5), 058001 (May 03, 2012). doi:10.1117/1.JBO.17.5.058001
History: Received December 24, 2011; Revised February 29, 2012; Accepted March 1, 2012
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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 AlPcS2a-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS2a (PDT effect), bleomycin (chemotherapy effect), or AlPcS2a+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 (1.5J/cm2 @ 5mW/cm2) AlPcS2a-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations—incubation of F98 cells in 0.1μg/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 1.5J/cm2 together with 0.25μg/ml bleomycin resulted in approximately 20% and 18% 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.

Figures in this Article
© 2012 Society of Photo-Optical Instrumentation Engineers

Citation

Marlon S. Mathews ; Joseph W. Blickenstaff ; En-Chung Shih ; Genesis Zamora ; Van Vo, et al.
"Photochemical internalization of bleomycin for glioma treatment", J. Biomed. Opt. 17(5), 058001 (May 03, 2012). ; http://dx.doi.org/10.1117/1.JBO.17.5.058001


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