Squaraine dyes for photodynamic therapy:: Mechanism of cytotoxicity and DNA damage induced by halogenated squaraine dyes plus light (>600 nm)

被引:46
作者
Ramaiah, D
Eckert, I
Arun, KT
Weidenfeller, L
Epe, B
机构
[1] Univ Mainz, Inst Pharm, D-55099 Mainz, Germany
[2] CSIR, Reg Res Lab, Photosci & Photon Div, Trivandrum 695019, Kerala, India
关键词
D O I
10.1111/j.1751-1097.2004.tb09863.x
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
Halogenated squaraine dyes 1 and 2 possess favorable photophysical and in vitro photobiological properties that make these new class of molecules interesting for photodynamic therapeutic applications. For a better understanding of the mechanism of their photobiological activity, we have analyzed the DNA damage and the cytotoxicity induced by these photosensitizers in mammalian cells and cell-free systems in the presence and absence of various additives and scavengers. Both photoactivated squaraines were found to be similar efficient in inducing single-strand breaks (SSB) in cell-free DNA when compared with the cellular DNA. Superoxide dismutase and catalase did not show any influence. However, the presence of tert-butanol and glutathione inhibited the formation of the DNA SSB, indicating an indirect (possibly squaraine radical mediated) mechanism under cell-free conditions. Replacing H2O in the buffer by D2O resulted in a five- to six-fold increase in the number of the SSB in cell-free DNA and a significant enhancement of the photocytotoxicity in mouse lymphoma cells. The results demonstrate that singlet oxygen is the major reactive species under cell-free and cellular conditions and confirm that squaraine-based sensitizers 1 and 2 can have potential applications in photodynamic therapy.
引用
收藏
页码:99 / 104
页数:6
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