A novel water-soluble phthalocyanine-based organic molecule for the effective NIR triggered dual phototherapy of cancer

Abstract

The use of photothermal therapy (PTT) synergized photodynamic therapy (PDT) is of significant importance for cancer theranostics when compared with monotherapy, and it shows a more promising future for use in clinical applications. Dual modal phototherapy has attracted increasing attention in recent years for the enhancement of cancer therapy efficacy, but it usually requires loading two or more types of ingredients and the use of inconvenient dual-laser irradiation combined within a single platform of treatment to realize difunctional performance. Herein, a difunctional theranostic agent based on a single versatile ionized copper phthalocyanine, Cu-1, was strategically synthesized, simultaneously integrating photothermal and photodynamic effects, and it showed ideal water dispersion abilities, intensive near infrared (NIR) absorbance, outstanding cytocompatibility, and robust photophysical performance for sufficient heat and singlet oxygen (¹O₂) generation. Cu-1 irradiated with a 730 nm laser created a prominent phototherapeutic effect, with high photothermal conversion (41.5%) and a high singlet oxygen quantum yield (32.3%). Intra-tumoral injection of such a photoconductive agent into 4T1 tumor-bearing mice followed by treatment with a single 730 nm NIR laser resulted in, from the in vivo therapy results, solid tumor growth of the mice being significantly inhibited, with the maximal destruction of the cancer cells and tissues, suggesting excellent anti-tumor efficacy as a result of the PTT/PDT combination therapy. Overall, this work based on a single Cu-1 approach obviously enhances the survival rates of tumor-bearing mice with maximized therapeutic outcomes, and it provides a new dimension for the design of highly efficient photosensitizers for clinical tumor therapy.