Photodynamic effect of carbon dots and aluminum chloride phthalocyanine against skin cancer: modulation by an autophagy inducer.

Photodynamic Therapy (PDT) is a therapeutic approach for several cancer types based on the photoactivation of photosensitizer (PS), leading to reactive oxygen species (ROS) generation and cancer cell death. Given that autophagy may exert cytoprotective or cytotoxic effects following PDT, modulation of autophagy-related pathways has attracted increasing research interest for improving therapeutic outcome. In this study, newly synthesized carbon dots (CDs) and commercially available aluminum chloride phthalocyanine (AlClPc) were employed as PSs individually or in combination with the autophagy-inducer monocarbonyl curcumin analogue C1 under different treatment protocols. CDs were synthesized based on a facile hydrothermal technique and characterized for their morphological, chemical, physicochemical and optical properties, showing intense blue fluorescence, and pronounced ROS generation ability. PDT studies revealed moderate light dose-dependent phototoxicity for CDs, whereas AlClPc presented significantly enhanced photodynamic activity. To investigate the influence of autophagy modulation on PDT response, pre-treatment, post-treatment, and co-incubation protocols with C1 were employed under 661 nm irradiation. Pre-treatment with C1 enhanced the PDT efficacy of CDs, while post-treatment and co-incubation protocols attenuated CDs-mediated phototoxicity, indicating a cytoprotective effect of C1. In contrast, all C1-containing treatment protocols improved the photodynamic performance of AlClPc. ROS generation studies further supported the observed biological responses. The present study highlights the dual role of autophagy modulation in PDT and demonstrates that C1 may either attenuate residual phototoxicity following CDs-mediated PDT or enhance the photodynamic efficacy of AlClPc, depending on the PS. These findings emphasize the potential of autophagy-related strategies for the optimization of PDT applications.