CD47-SIRPα axis in cancer therapy: precise delivery of CD47-targeted therapeutics and design of anti-phagocytic drug delivery systems
CD47-SIRPα axis in cancer therapy: precise delivery of CD47-targeted therapeutics and design of anti-phagocytic drug delivery systems
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DOI：
10.1016/j.medidd.2022.100139
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发表时间：
2022-06
影响因子：
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通讯作者：
Junqiao Zhu;Chengyuan Cai;Jia-xiang Li;Jisheng Xiao;Xiaopin Duan
中科院分区：
文献类型：
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作者：
Junqiao Zhu;Chengyuan Cai;Jia-xiang Li;Jisheng Xiao;Xiaopin Duan
CD47作为一种“自我标记”，在人类、小鼠和其他哺乳动物的所有细胞表面表达，通过与巨噬细胞和树突状细胞上的信号调节蛋白α (SIRPα)相互作用，发出“不要吃我”的信号，抑制正常细胞的吞噬破坏。不幸的是，多种类型的癌细胞利用这种“不要吃我”的信号，通过在其表面过度表达CD47来逃避巨噬细胞的识别并避免免疫监视。因此，阻断CD47-SIRPα轴可能是癌症治疗的一个有希望的治疗靶点。然而，由于CD47在正常组织中广泛表达，CD47靶向治疗很可能引起贫血等严重的副作用，因此，CD47靶向治疗的精确递送是提高临床疗效和减少副作用的关键部分。此外，“不要吃我”的信号也可以用来设计抗吞噬药物递送系统，以延长血液循环时间和肿瘤部位的积累。本文主要从CD47- sirp α轴在肿瘤治疗中的作用两方面进行综述，一是通过精心设计的递送系统准确递送CD47靶向治疗药物，二是合理设计基于CD47的抗吞噬药物递送系统。
As a “marker of self”, CD47 is expressed on the surface of all cells in humans, mice, and other mammals to inhibit phagocytic destruction of normal cells through interacting with signal regulatory protein α (SIRPα) on the macrophages and dendritic cells and sending a “don’t eat me” signal. Unfortunately, multiple types of cancer cells take advantage of this “don’t eat me” signal by overexpressing CD47 on their surface to evade recognition by the macrophages and avoid immune surveillance. Thus, the blockage of the CD47-SIRPα axis may be a promising therapeutic target for cancer therapy. However, CD47-targeted therapies can most likely cause serious side effects such as anemia due to the widespread expression of CD47 in normal tissues, thereby, the precise delivery of CD47-targeted therapeutics is a key part in increasing clinical efficacies and reducing side effects. In addition, the “don’t eat me” signal can also be exploited to design anti-phagocytic drug delivery systems to enhance circulation time in blood and accumulation in tumor sites. In this review, we focus on the two parts of CD47-SIRPα axis in the tumor therapy, one is the accurate delivery of CD47-targeted therapeutics by well-designed delivery systems, the other is the rational design of CD47 based anti-phagocytic drug delivery systems.