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Proceedings Paper

Photochemical internalization for the treatment of malignant gliomas
Author(s): Steen J. Madsen; Khishigzaya Kharkhuu; Kristian Berg; Henry Hirschberg
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Paper Abstract

Photochemical internalization (PCI) is a technique to improve the utilization of macromolecules (e.g. chemotherapeutic agents) in cancer therapy in a site-specific manner. The concept is based on the use of specially designed photosensitizers which localize preferentially in the membranes of endocytic vesicles. Upon exposure to light the photosensitizers induce the formation of reactive oxygen species such as singlet molecular oxygen. The photooxidation of the endocytic membranes leads to the release of the contents of the vesicles into the cytosol. In this way, macromolecules encapsulated by the vesicles will reach the cytosol and exert their biological activity instead of being degraded by lysosomal hydrolases. The utility of PCI for the treatment of malignant gliomas was investigated in vitro using an F98 rat glioma cell line. The cytotoxicity of 5-aminolevulinic acid (ALA) based PCI of bleomycin was compared to: (1) ALA-PDT, and (2) bleomycin. In all cases, monolayers were incubated in ALA, bleomycin, or ALA + bleomycin for 4 hours and were subsequently exposed to 635 nm light. Toxicity was evaluated using colony formation assays. F98 rat glioma cells in monolayer were found to be susceptible to the effects of both ALA-PDT and bleomycin. ALA-PDT was found to be particularly effective when light was delivered at a low irradiance of 5 mW cm-2. In this case, a radiant exposure of 20 J cm-2 resulted in only 4% survival. Bleomycin was found to be toxic at relatively low concentrations, incubation of F98 cells in 10 &mgr;g ml-1 for 4 hours resulted in 1% survival. The PCI effect was found to be negligible for the parameters investigated in the F98 cell line suggesting that: (1) the incubation time was sub-optimal and/or (2) ALA was inappropriate for this application.

Paper Details

Date Published: 23 March 2007
PDF: 6 pages
Proc. SPIE 6424, Photonic Therapeutics and Diagnostics III, 64242C (23 March 2007); doi: 10.1117/12.705086
Show Author Affiliations
Steen J. Madsen, Univ. of Nevada/Las Vegas (United States)
Univ. of Nevada/Las Vegas Institute of Cellular and Molecular Medicine (United States)
Khishigzaya Kharkhuu, Univ. of Nevada/Las Vegas (United States)
Kristian Berg, Rikshospitalet/Radiumhospital (Norway)
Henry Hirschberg, Univ. of Nevada/Las Vegas (United States)
Beckman Laser Institute, Univ. of California/Irvine (United States)


Published in SPIE Proceedings Vol. 6424:
Photonic Therapeutics and Diagnostics III
Henry Hirschberg; Steen J. Madsen; Brian Jet-Fei Wong; Justus F. R. Ilgner; Reza S. Malek; Kenton W. Gregory; Guillermo J. Tearney; Nikiforos Kollias; Bernard Choi; Haishan Zeng, Editor(s)

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