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Phthalocyanine-based photosensitizer with tumor-pH-responsive properties for cancer theranostics
Shufeng Yan1, Jincan Chen, Liangzhi Cai
1State Key Laboratory of Structural Chemistry, and CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China. HMD_lab@fzu.edu.cn zchen@fjirsm.ac.cn.
Abstract:
Photodynamic therapy (PDT) has attracted attention for its potential for tumor destruction. We herein report a pH-responsive photosensitizer, synthesized by conjugating zinc phthalocyanine (ZnPc) with 2,4,6-tris(N,N-dimethylaminomethyl) phenoxy (TAP), which exhibited high phototoxicity at pH 6.5 (slightly acidic condition as in the extracellular tumor microenvironment) but no obvious phototoxicity at physiological pH 7.4. This pH-responsive photosensitizer specifically destroyed mouse mammary carcinoma cells 4T1 with an IC50 of 0.20 μM under a relatively low light dosage (2.5 J cm-2). The subsequent in vivo studies using 4T1-bearing mice demonstrated that this tumor-targeting photosensitizer ZnPc(TAP)4 not only ablated tumor cells photodynamically but also presented clear fluorescence cell imaging of tumor sites. These findings suggest that such a tumor-pH-responsive photosensitizer based on phthalocyanine may open up a new avenue for tumor-targeted and image-guided cancer theranostics in PDT.
