靶向分化群47-信号调节蛋白α的抗肿瘤药物递送系统研究进展

Research Progress of Anti-tumor Drug Delivery Systems Based on CD47-SIRPα Axis

巨噬细胞是肿瘤微环境的重要组成部分,肿瘤细胞通过表达分化群47(CD47)与巨噬细胞受体信号调节蛋白α(SIRPα)相互作用而避免被吞噬。目前通过阻断CD47-SIRPα的相互作用进而恢复巨噬细胞吞噬功能的研究已经受到了广泛关注,包括抗CD47抗体在内的多种药物已经开展了临床试验研究。然而常见的血液毒性限制了这类药物的临床应用,除了筛选肿瘤特异性结合的药物外,通过药物递送系统包载CD47抑制剂用于肿瘤的治疗是一种有效策略。通过以CD47-SIRPα的结构和信号通路为基础,详细综述了靶向CD47-SIRPα的递送系统,包括白蛋白、脂质等不同载体材料构建的纳米递送系统,凝胶递送系统和抗体偶联药物等,以期为临床药物开发提供借鉴。

Macrophages are an important part of tumor microenvironment, and tumor cells avoid phagocytosis by expressing CD47to interact with SIRPα on the surface of macrophages. At present, the researches on restoring the phagocytic function of macrophages by blocking the interaction of CD47-SIRPα axis have received widespread attention, and a variety of drugs including anti-CD47 antibodies have been put to clinical trials. However, common hematological toxicity has limited the clinical application of these drugs. In addition to screening out drugs that specifically act on tumor cells, encapsulating CD47 inhibitors through drug delivery systems is an effective strategy for tumor treatment. Based on the structure and signaling pathway of CD47-SIRPα axis, this review summarizes the delivery systems targeting CD47-SIRPα axis, including gel matrix, antibody-drug conjugates and nano-delivery systems constructed by different carrier materials, in order to provide reference for clinical development of drugs.