Au Nanoclusters and Photosensitizer Dual Loaded Spatiotemporal Controllable Liposomal Nanocomposites Enhance Tumor Photodynamic Therapy Effect by Inhibiting Thioredoxin Reductase

Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure of tumors with high selectivity and low side effect. However, it is usually not efficient in long-lasting tumor control. One of the main reasons is tumor cells develop some protective mechanisms that help them to deal with oxidative stress in the environment. The thioredoxin system in cancer is an important antioxidant defense system. Au nanoclusters could effectively inhibit thioredoxin reductase (TrxR) in tumor cell cytoplasm. Herein, Au nanoclusters and photosensitizer Chlorine 6 (Ce6) are co-loaded in spatiotemporal controllable liposomal nanocomposites. pH responsive molecule inserted in lipid bilayer greatly contributes to the instability of the lipid membrane in lysosomal at low pH environment. Then the payloads can rapidly release into cytoplasm. Au nanoclusters effectively inhibit TrxR in cytoplasm and enhance the photodynamic-induced intracellular reactive oxygen-free radical concentration, improving the effect of PDT. Breast cancer is chosen as a tumor model and the Au nanoclusters and photosensitizer co-loaded liposomal nanocomposites are studied to improve the effect of PDT both in vitro and in vivo, and its corresponding mechanism is investigated. This study develops a new application of gold nanoclusters and provides a new train of thoughts for enhancing the effect of PDT.