A Tumor-pH-Responsive Supramolecular Photosensitizer for Activatable Photodynamic Therapy with Minimal <i>In Vivo</i> Skin Phototoxicity

Abstract

A major challenge in photodynamic therapy (PDT) is the development of new tumor-targeting photosensitizers. The tumor-specific activation is considered to be an effective strategy for designing these photosensitizers. Herein, we describe a novel tumor-pH-responsive supramolecular photosensitizer, LDH-ZnPcS₈, which is not photoactive under neutral conditions but is precisely and efficiently activated in a slightly acidic environment (pH 6.5). LDH-ZnPcS₈ is prepared by using a simple coprecipitation method based on the electrostatic interaction between negatively charged octasulfonate-modified zinc(II) phthalocyanine (ZnPcS₈) and cationic hydroxide layers of layered double hydroxide (LDH). The <i>in vitro</i> photodynamic activities of LDH-ZnPcS₈ in cancer cells are dramatically enhanced relative to those of ZnPcS₈ alone. The results of <i>in vivo</i> fluorescence imaging demonstrate that the nanohybrid is activated in tumor tissues, where it displays an excellent PDT effect resulting in 95.3% tumor growth inhibition. Furthermore, the minimal skin phototoxicity of LDH-ZnPcS₈ highlights its high potential as a novel photosensitizer for activatable PDT.