Spectroscopic studies of photobleaching and photoproduct formation of meta(tetrahydroxyphenyl) chlorin (m-THPC) used in photodynamic therapy.: The production of singlet oxygen by m-THPC

被引:117
作者
Hadjur, C
Lange, N [1 ]
Rebstein, J
Monnier, P
van den Bergh, H
Wagnières, G
机构
[1] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Inst Environm Engn, CH-1015 Lausanne, Switzerland
[2] CHUV Hosp, Dept Otolaryngol Head & Neck Surg, CH-1011 Lausanne, Switzerland
关键词
meta(tetrahydoxyphenyl)chlorin (m-THPC); photosensitizers; photodynamic therapy (PDT); photobleaching; photoproducts; spectroscopy; quantum yield; singlet oxygen;
D O I
10.1016/S1011-1344(98)00177-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Meta(tetrahydroxyphenyl)chlorin (m-THPC) is a new photosensitizer currently undergoing clinical trials at Lausanne's CHUV hospital for photodynamic therapy (PDT) of early cancer in the upper aerodigestive tract. The illumination of m-THPC with light at 650 nn in aqueous solution containing 10% foetal calf serum (FCS) causes two simultaneously occurring processes: its photodegradation and the formation of a more stable photoproduct absorbing at 320 mn. The photodegradation quantum yield (Phi(Pb)) of m-THPC is found to be of the order of 1.5 x 10(-5) in 10% FCS. A strong dependence on oxygen concentration of the photodegradation and the formation of photoproducts has been observed. Indeed, the m-THPC presents rather low Phi(Pb) under Nz-saturated conditions: 6.9 x 10(-6). In aerobic conditions, the photodegradation as well as the formation of photoproducts, have been competitively inhibited by known singlet oxygen (O-1(2)) quenchers. The addition of superoxide dismutase (SOD), catalase or desferal, known quenching agents of type I mechanisms, has little or no effect on the rate of photobleaching and photoproduct formation of m-THPC. m-THPC generates O-1(2) With a quantum yield of 0.3 in ethanol solution as determined by photo-oxidation experiments using 1,3-diphenylisobenzofuran (DPBF) as substrate. The rate and quantum yield of DPBF photo-oxidation are found to increase with increasing substrate concentration and decrease in phosphate buffer solution (Phi(Delta) = 0.01), due to the partially hydrophilic character of m-THPC. In addition, the reaction of O-1(2) with TEMP (2,2,6,6-tetramethyl-4-piperidone) in combination with electron paramagnetic resonance (EPR) detection has been used to determine the formation of O-1(2) by m-THPC in ethanol solution. (C) 1998 Elsevier Science S.A. All rights reserved.
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页码:170 / 178
页数:9
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