Activation of scramblases is one of the mechanisms that regulates the exposure of phosphatidylserine to the cell surface, a process that plays an important role in tumour immunosuppression. Here we show that chemotherapeutic agents induce overexpression of Xkr8, a scramblase activated during apoptosis, at the transcriptional level in cancer cells, both in vitro and in vivo. Based on this finding, we developed a nanocarrier for co-delivery of Xkr8 short interfering RNA and the FuOXP prodrug to tumours. Intravenous injection of our nanocarrier led to significant inhibition of tumour growth in colon and pancreatic cancer models along with increased antitumour immune response. Targeting Xkr8 in combination with chemotherapy may represent a novel strategy for the treatment of various types of cancers.

扰乱酶的激活是调节磷脂酰丝氨酸暴露于细胞表面的机制之一，这一过程在肿瘤免疫抑制中发挥重要作用。在这里，我们发现化疗药物在体外和体内的癌细胞转录水平上诱导 Xkr8（一种在细胞凋亡过程中激活的扰乱酶）过度表达。基于这一发现，我们开发了一种纳米载体，用于将 Xkr8 短干扰 RNA 和 FuOXP 前药共同递送至肿瘤。静脉注射我们的纳米载体可显着抑制结肠癌和胰腺癌模型中的肿瘤生长，并增强抗肿瘤免疫反应。靶向 Xkr8 与化疗相结合可能代表了治疗各种类型癌症的新策略。