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4B-P-8
BIOMEDICAL PHOTONICS
Photobleaching of cationic porphyrins and their complexes with folic acid in presence of L-histidine and D-mannitol as quenchers
L. Mkrtchyan1, A. Zakoyan1, T. Seferyan1, G. Gyulkhandanyan1, V. Tuchin2
1-Institute of Biochemistry, NAS of Armenia, 5/1, P. Sevak st., Yerevan 0014, Armenia 2- Saratov State University, Science Medical Center, 83, Astrakhanskaya st., Saratov 410012, Russia Main author email address:mkrtchyanlusine709@gmail.com
Photodynamic therapy (PDT) is an efficient treatment of tumors, and based on the interaction between suitable wavelength of light and a photosensitizer (PS) with the presence of oxygen to produce toxicity [1].
Compared to healthy cells, multiple kinds of tumor cells express high levels of folate receptors (FRs) on their surface [2]. FRa is overexpressed in a large number of cancers of epithelial origin (e.g. breast, lung, kidney and ovarian cancers). The expression in these carcinomas being 100-300 times higher than on healthy cells and in the order of 1-10 million receptor copies per cell [3]. Therefore, it is a promising strategy to improve the effectiveness of PDT by binding PS's with folic acid (FA).
Photobleaching can be defined as the loss of absorption or emission intensity that is caused by light [1]. It is commonly accepted that more stable PS the better it will perform, mainly because it can endure more cycles of singlet oxygen (1O2) production [4]. Therefore, in this work we obtain the non-covalent complexes of FA and porphyrins as PS's to improve the targeted nature of PDT. Also, the photobleaching of three cationic porphyrins (TOEt4PyP, Zn-TOEt4PyP and Zn-TBut3PyP) and their complexes with FA was studied. The photobleaching of complexes and their components were performed in presence of two quenchers: L-histidine and D-mannitol. It is known that L-histidine is a singlet oxygen quencher and D-mannitol is a free radicals' quencher (mainly, mannitol combines with •OH radical producing water molecule) [1]. Deferent concentrations of these quenchers were tested and it was shown that the mannitol concentration (0.8 mM) that is needed for effective quenching and for decrease of photobleaching rate after 30 min of illumination by tungsten lamp is 10 times higher than the concentration for histidine (0.08 mM). It is also noted that further increase of quenchers' concentration to 10 mM for mannitol and to 1 mM for histidine has the reverse effect as the photobleaching was more intense. Histidine was more effective quencher for Zn-TBut3PyP and for its complex with FA. Mannitol was shown to be more effective for TOEt4PyP and Zn-TOEt4PyP than histidine. The more effective photoprotection by his-tidine for Zn-TBut3PyP is correlated with higher singlet oxygen quantum yield of this PS (yA=0,98) compared with other two PS's (ya=0,7 for TOEt4PyP and yA=0,84 for Zn-TBut3PyP). It should be noted that both quenchers has a protective effect, thus indicating that both singlet oxygen and free radicals play a crucial role in the photobleaching mechanism of these cationic porphyrins.
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