A Dual Activatable Photosensitizer toward Targeted Photodynamic Therapy
A Dual Activatable Photosensitizer toward Targeted Photodynamic Therapy
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DOI：
10.1021/jm500456e
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发表时间：
2014-05-22
影响因子：
7.3
通讯作者：
Ng, Dennis K. P.
中科院分区：
文献类型：
--
作者：
Lau, Janet T. F.;Lo, Pui-Chi;Ng, Dennis K. P.
合成了一种不对称的双二茂铁基硅酞菁，其中二硫键和腙键可分别被二硫苏糖醇和酸裂解。二茂铁基猝灭剂和酞菁核的分离大大增强了荧光发射、单线态氧产生、细胞内荧光强度和体外光细胞毒性。的结果进行了比较，为两个对称的类似物，其中包含二硫化物或腙连接，因此只能被激活这些刺激之一。对于双重可活化剂，在微酸性环境（pH = 4.5-6.8）下和在二硫苏糖醇（在毫摩尔范围内）存在下可以获得最大的增强，所述二硫苏糖醇可以大致模拟肿瘤组织的酸性和还原环境。该化合物也可以在荷瘤裸鼠中活化。它在肿瘤内注射后的前10小时内表现出肿瘤中荧光强度的增加，并且在照射时可以有效地抑制肿瘤的生长。
An unsymmetrical bisferrocenyl silicon(IV) phthalocyanine has been prepared in which the disulfide and hydrazone linkers can be cleaved by dithiothreitol and acid, respectively. The separation of the ferrocenyl quenchers and the phthalocyanine core greatly enhances the fluorescence emission, singlet oxygen production, intracellular fluorescence intensity, and in vitro photocytotoxicity. The results have been compared with those for the two symmetrical analogues which contain either the disulfide or hydrazone linker and therefore can only be activated by one of these stimuli. For the dual activatable agent, the greatest enhancement can be attained under a slightly acidic environment (pH = 4.5-6.8) and in the presence of dithiothreitol (in millimolar range), which can roughly mimic the acidic and reducing environment of tumor tissues. This compound can also be activated in tumor-bearing nude mice. It exhibits an increase in fluorescence intensity in the tumor over the first 10 h after intratumoral injection and can effectively inhibit the growth of tumor upon illumination.