Concurrent photothermal therapy and photodynamic therapy for cutaneous squamous cell carcinoma by gold nanoclusters under a single NIR laser irradiation
Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has become a promising therapeutic technique for the treatment of skin cancers because of its minial invasiveness, high efficacy and low side effects. Nevertheless, a single modality therapy either PTT or PDT has limited clinical effectiveness in treating skin cancers. Combined applications of PTT and PDT have been frequently reported; however PTT and PDT often require their respective photoagents and excitation light sources, resulting in challenges in clinical transformation. In this study, to address these issues, we report the use of a biocompatible gold nanoclusters Au25(Capt)18 for concurrent PTT and PDT treatment of cutaneous squamous cell carcinoma (cSCC) using an 808 nm near-infrared (NIR) laser. Utilizing their high light-thermal conversion efficiency, potent generation of singlet oxygen and strong photothermal stability, Au25(Capt)18 nanoclusters potentiated a significant proliferation suppression on cSCC XL50 cells in vitro and inhibition of cSCC tumors on SKH-1 mice in vivo. In particular, under the 808 nm light irradiation, the tumor cell killing contributions of PTT and PDT were estimated to be 28.86% and 71.14%, respectively, by using ROS scavenger to quench the PDT effect. Tumor-infiltrating CD4+ T and CD8+ T cells were observed after one course of concurrent PTT and PDT. Preliminary toxicity studies indicate low adverse effects of Au25(Capt)18 nanoclusters. Our work reports the use of a simple nanostructure for simultaneous PTT and PDT applications to effectively kill cSCC and to induce anti-tumor immune responses. Our work could lead to the development of effective photoagents for current, synergistic applications of different phototherapies with targeted immunological responses for treatment of cancers.