Brasseur N, Nguyen T L, Langlois R, Ouellet R, Marengo S, Houde D, van Lier J E
MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
J Med Chem. 1994 Feb 4;37(3):415-20. doi: 10.1021/jm00029a014.
Bis(tert-butyldimethylsiloxy)- (7), bis(dimethylthexylsiloxy)- (8), bis(tri-n-hexylsiloxy)- (9), and bis(dimethyloctadecylsiloxy)silicon 2,3-naphthalocyanines (10) were prepared via substitution of the bis(hydroxy) precursor with the corresponding chlorosilane ligands and characterized by spectroscopic and combustion analyses. They show strong absorption around 780 nm where tissues exhibit optimal transparency. Compounds 7-10 are capable of producing singlet oxygen. They are relatively photostable although less stable than the analogous phthalocyanine, i.e., the bis-(dimethylthexylsiloxy)silicon phthalocyanine (12). They were evaluated as potential photosensitizers for the photodynamic therapy (PDT) of cancer in vitro against V-79 cells and in vivo against the EMT-6 tumor in Balb/c mice. In vitro all four dyes showed limited phototoxicity combined with substantial dark toxicity. Surprisingly, in vivo (i.v., 0.1 mumol/kg, 24 h prior to the photoirradiation of the tumor with 780-nm light, 190 mW/cm2, 400 J/cm2) all dyes induced tumor regression in at least 50% of mice whereas compound 8 gave a complete tumor response in 80% of mice without apparent systemic toxicity at doses as high as 10 mumol/kg. At 24 h postinjection, compound 8 showed a favorable tumor to muscle ratio of 7, assuring minimal damage to the healthy tissue surrounding the tumor during PDT. Our data confirm the potential of silicon naphthalocyanines as far-red-shifted photosensitizers for the PDT of cancer and indicate the importance of the selection of the two axial silicon ligands for optimal photodynamic efficacy.
通过用相应的氯硅烷配体取代双羟基前体，制备了双（叔丁基二甲基硅氧基） - （7）、双（二甲基叔己基硅氧基） - （8）、双（三正己基硅氧基） - （9）和双（二甲基十八烷基硅氧基）硅2,3 - 萘酞菁（10），并通过光谱和燃烧分析对其进行了表征。它们在780 nm左右显示出强烈吸收，而组织在该波长处具有最佳透明度。化合物7 - 10能够产生单线态氧。它们相对光稳定，尽管比类似的酞菁，即双（二甲基叔己基硅氧基）硅酞菁（12）稳定性稍差。对它们作为癌症光动力疗法（PDT）的潜在光敏剂进行了评估，在体外针对V - 79细胞，在体内针对Balb / c小鼠的EMT - 6肿瘤。在体外，所有四种染料都表现出有限的光毒性并伴有明显的暗毒性。令人惊讶的是，在体内（静脉注射，0.1 μmol / kg，在用780 - nm光照射肿瘤前24小时，190 mW / cm²，400 J / cm²），所有染料在至少50%的小鼠中诱导肿瘤消退，而化合物8在高达10 μmol / kg的剂量下，在80%的小鼠中产生完全肿瘤反应且无明显全身毒性。在注射后24小时，化合物8显示出良好的肿瘤与肌肉比为7，确保在PDT期间对肿瘤周围健康组织的损伤最小。我们的数据证实了硅萘酞菁作为用于癌症PDT的远红移光敏剂的潜力，并表明选择两个轴向硅配体对于最佳光动力疗效的重要性。
