[Frontiers in Bioscience 16, 208-224, January 1, 2011]

Approaches to improve photodynamic therapy of cancer

Malgorzata Firczuk1, Magdalena Winiarska1, Angelika Szokalska1, Malgorzata Jodlowska1, Marta Swiech1, Kamil Bojarczuk1, Pawel Salwa1, Dominika Nowis1

1Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1A F building, 02-097 Warsaw, Poland

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Major advantages and disadvantages of PDT - what needs improvement or might be improved?
4. New photosensitizers
5. New light sources
6. Targeting cytoprotective mechanisms in PDT-treated cells
6.1. ROS-scavenging enzymes
6.2. Handling of damaged proteins
6.3. Mechanisms not directly associated with ROS scavenging
7. Combinations of PDT with other treatment modalities
8. Enhancement of PDT-mediated immune response
8.1. Immunoadjuvants
8.2. Cytokines
8.3. Adoptive immunotherapy
8.4. Introduction of foreign antigens
8.5. Anticancer therapeutics
9. Other new directions
9.1. Photochemical internalization
9.2. Metronomic PDT
9.3. Nanoparticle-based PDT
9.4. Two photon PDT
10. Conclusions
11. Acknowledgments
12. References

1. ABSTRACT

Photodynamic therapy (PDT) is a clinically approved method of tumor treatment. Its unique mechanism of action results from minimal invasiveness and high selectivity towards transformed cells. However, visible light used to excite most photosensitizers has rather limited ability to penetrate tissues resulting in insufficient destruction of deeply seated malignant cells. Therefore, novel strategies for further potentiation of the anticancer effectiveness of PDT have been developed. These include combined treatments with surgery, chemo- and radiotherapy, strategies targeting cytoprotective mechanisms induced in PDT-treated cells, as well as attempts aimed at enhancement of PDT-mediated antitumor immune response. Moreover, new photosensitizers and novel light sources are being developed. Impressive progress in nanotechnology and understanding of tumor cell biology rise hopes for further improvements in this elegant and promising method of cancer treatment.