转录因子EB（TFEB）是调控自噬和溶酶体生成的重要调控因子，当细胞处于饥饿等状态时，主要分布于细胞质中的TFEB转移到细胞核内，导致一系列与自噬相关的基因表达上调。我们前期研究显示，纳米银颗粒可以显著上调细胞自噬水平，体外和体内实验都表明抑制自噬可以增强纳米银对肿瘤的杀伤。我们后续研究发现纳米银引起自噬是通过诱导TFEB进核导致的，并且TFEB siRNA处理可以显著增强纳米银对肿瘤细胞的杀伤效果。我们试图从调控TFEB进核的机制探究出发，寻找更为有效的抑制纳米材料保护性自噬的方法。结果显示纳米银与饥饿等其他自噬诱导因素引起TFEB进核的机制不同。所以我们接下来需要找到导致TFEB进核的关键修饰位点，以及对TFEB进行修饰，促进其进核的上游激酶。然后将TFEB进核的抑制手段与纳米银联用，在体内外验证这种联合药物的抗肿瘤效果。这可能是一种特异性更强的增强纳米银抗肿瘤效果的联合给药方法。

Transcription factor EB (TFEB) is an master regulator of autophagy and lysosomal biogenesis. When cell was starved, the TFEB which mainly distributed in the cytoplasm translocated to the nucleus and enhanced the expression of a serious of autophagy-related genes. In our previous study, we have reported that silver nanoparticles (Ag NPs) induced autophagy in cancer cells and inhibit that autophagy improved the efficacy of Ag NPs in anti-cancer therapy in vivo and in vitro. Our present study found that the autophagy induced by Ag NPs was caused by inducing TFEB translocation to the nucleus. And TFEB siRNA co-treatment also dramatically enhanced the tumor killing activity of Ag NPs. .We tried to find a more specific way to inhibit the Ag NPs induced- autophagy by exploring the pathway which regulated the translocation of TFEB. And we found the mechanism of TFEB translocation to the nucleus induced by Ag NPs treatment was different from the mechanism by other autophagy inducer treatment, such as starvation. So next we need to do firstly is finding the key modification sites and the kinase which cause TFEB translocation to the nucleus by Ag NPs treatment. Then, we should verify the anti-tumor efficiency of Ag NPs by co-treating with TFEB translocation inhibitor in vitro and in vivo. Inhibition of TFEB translocation may be a more useful strategy for improving the efficacy of Ag NPs in anti-cancer therapy.