Phthalocyanine-based photosensitizer with tumor-pH-responsive properties for cancer theranostics

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 IC 50 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. A versatile phthalocyanine-based photosensitizer with tumor-pH-responsive properties for cancer theranostics.