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BioMed Research International
Volume 2014 (2014), Article ID 921296, 10 pages
http://dx.doi.org/10.1155/2014/921296
Research Article

Enhanced Efficacy of Bleomycin in Bladder Cancer Cells by Photochemical Internalization

1Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, P.O. Box 8905, 7491 Trondheim, Norway
2PCI Biotech AS, Strandveien 55, 1366 Lysaker, Norway
3APIM Therapeutics AS, Sem Sælandsvei 14, 7084 Trondheim, Norway

Received 8 March 2014; Revised 29 May 2014; Accepted 29 May 2014; Published 30 June 2014

Academic Editor: Swaran J. S. Flora

Copyright © 2014 Yan Baglo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI) was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27), as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) and blue light (435 nm). Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not.