光动力治疗是选择性高、副作用小的微创肿瘤治疗方法，然而在长期的肿瘤控制中，它通常不是非常有效。其中最主要的一个原因是肿瘤细胞对氧化应激环境发展的一些保护性机制。硫氧还蛋白系统是很重要的抗氧化防御系统，我们之前的研究发现金纳米团簇能有效抑制肿瘤细胞内的硫氧还蛋白还原酶（TrxR）。在这个研究中我们将金纳米团簇和光敏剂Ce6共同负载于一种时空可控型脂质纳米复合体，pH响应性分子嵌入脂质双层中，在溶酶体低pH环境下引发脂质膜不稳定，使负载的药物快速释放，金纳米团簇有效抑制胞浆中TrxR，提高光动力学引发的细胞内活性氧自由基浓度，增强光动力治疗效应。脂质纳米复合体表面偶联有肿瘤靶向的Her-2抗体，能提高肿瘤特异性空间分布。我们选择乳腺癌为模型，通过体外和体内实验研究金纳米团簇和光敏剂双负载脂质纳米复合体增强光动力治疗效应及其相应的机制，为光动力学治疗作为低毒高效的新方法在长期的肿瘤控制中提供新思

Photodynamic therapy is a minimally invasive treatment method of tumors with high selectivity and little 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 cope with oxidative stress in the environment. The thioredoxin system in cancer is an important antioxidant defense system. Our previous study found that Au nanoclusters could effectively inhibit thioredoxin reductase (TrxR) in tumor cell cytoplasm. In this study, Au nanoclusters and photosensitizer Chlorine 6 (Ce6) were co-loaded in spatio-temporal controllable liposomal nanocomposites. pH responsive molecular inserted in lipid bilayer greatly contributed to the destabilization of the lipid membrane in lysosomal low pH environment, followed by the rapid release of the payloads. Au nanoclusters effectively inhibited TrxR in cytoplasm and improved the photodynamic induced intracellular reactive oxygen free radical concentration, improved the effect of photodynamic therapy (PDT). The surface of liposomal nanocomposites was conjugated with tumor targeting Her-2 antibody to improve tumor specific spatial distribution. We chose breast cancer as tumor model and studied the Au nanoclusters and photosensitizer co-loaded liposomal nanocomposites improved the effect of photodynamic therapy both in vitro and in vivo and its corresponding mechanism. Our study results will provide new train of thought for photodynamic therapy in long-lasting tumor control as a new method with low toxicity and high efficiency.