ISSN 1054-660X, Laser Physics, 2009, Vol. 19, No. 7, pp. 1–6. © Pleiades Publishing, Ltd., 2009. Original Russian Text © Astro, Ltd., 2009. 1 1 1. INTRODUCTION Photodynamic therapy (PDT) is a relatively novel treatment modality for cancers as well as a variety of nononcologic applications [1–5]. This therapy is based on selective accumulation of photosensitizing agents in malignant tumors and is a method showing significant promise in tumor therapy [1–3]. Lower extracellular pH tumors as compared to normal tissues have been proposed to be a factor contributing to the tumor selective uptake of several photosensitizers [6– 11]. Many other contributing factors have been sug- gested, as cellular specificity and extracellular tumor characteristics as well [7]. This difference between solid tumors and surrounding normal tissue are related 1 The article is published in the original. to nutritional and metabolic factors, but the inade- quate functional vasculature is the main cause for an acidic microenvironment, a lower interstitial pH in malignant compared with normal tissue [10]. How- ever, the selectivity of porphyrins by tumors has been recognized for about 60 years, and several hypotheses have been put forward [7]. One hypotheses well accepted is that the most part of photosensitizers, mainly porphyrins are carried by lipoprotein recep- tors, type of receptor present in the most part of tumors cells due to high catabolism of cholesterol by these cells [12]. However, in addition to tissue proper- ties, the nature of the photosensitizer is important, mainly because the cellular drug uptake and dye distri- bution depend on physicochemical properties of the LASER METHODS AND CHEMISTRY, BIOLOGY, AND MEDICINE Influence of pH on the Phototransformation Process of Photogem 1 P. F. C. Menezes a, b, *, H. Imasato b , V. S. Bagnato a , Cl. H. Sibata c , J.R. Perussi b a Instituto de Quimica de Sao Carlos b Instituto de Fisica de Sao Carlos–University of Sao Paulo, Av. Trabalhador Sr ocarlense, 400, CEP: 13560-970-Sao Carlos SP, Brazil c Department of Radiation Oncology, Leo Jenkins Cancer Center, Brody School of Medicine, East Carolina University, Greenville, USA *e-mail: priscilamene@gmail.com Received January 26, 2009; in final form, February 1, 2009 Abstract—Photogem  is a hematoporphyrin derivative that has been used as a photosensitizer in experimen- tal and clinical Photodynamic Therapy (PDT) in Brazil. Photosensitizers are degraded under illumination. This process, usually called photobleaching, can be monitored by the decrease in fluorescence intensities and includes the following photoprocesses: photodegradation, phototransformation, and photorelocalisation. Photobleaching of hematoporphyrin-type sensitizers during illumination in aqueous solution is related not only to photodegradation but is also followed by the formation of photoproducts with a new fluorescence band at around 640–650 nm and with increased light absorption in the red spectral region at 640 nm. In this study, the influence of pH on the phototransformation process was investigated. Photogem  solutions, 40 μg/ml, were irradiated with 514 nm with intensity of 100 mW/cm 2 for 20 min with different pHs environ- ment. The controls were performed with the samples in the absence of light. The Photogem  photodegrada- tion is dependent on the pH. The behavior of photodegradation and photoproducts formation (monitored at 640 nm) is distinct and depends on the photosensitizer concentration. The processes of degradation and pho- toproducts formation were monitored with Photogem  in the concentration of 40 μg/mL since that demon- strated the best visualization of both processes. While below pH 5 the photodegradation occurred, there was no detectable presence of photoproducts. The increase of pH led to increase of the rate of formation of pho- toproducts with photodegradation reaching the highest value at pH 10. The increase of photoproducts for- mation and instability of Photogem  from pH 6 to pH 10 are in agreement with the desired properties of an ideal photosensitizer since there are significant differences in pH between normal (7.0 < pH < 8.6) and tumor (5.8 < pH < 7.9) tissues. It is important to know the effect of pH in the process of phototransformation (deg- radation and photoproduct formation) of the molecule since low pH values promotes increase in the propor- tion of aggregates species in solution and high pH values promotes increase in the proportion of monomeric species. There must be an ideal interval of pH which favors the phototransformation process that is correlated with the oxygen singlet formation responsible by the photodynamic effect. These differences of pH between normal and tumor cells can explain the presence of photosensitizers target in tumor cells, leading PDT to be a selective therapy. PACS numbers: @@@@ DOI: 10.1134/S1054660X0907@@@@