Zhao Manhan, Zhou Liming, Zhai Yifei, Sun Aiqin, Shao Genbao, Lin Qiong
School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China.
Biomolecules. 2025 Jun 26;15(7):936. doi: 10.3390/biom15070936.
Macropinocytosis is a non-selective, clathrin-independent endocytic process that facilitates bulk internalization of extracellular fluid and its dissolved components (including proteins, lipids, and nucleotides) through plasma membrane remodeling and the subsequent formation of macropinosomes. This evolutionarily conserved cellular process plays important roles in nutrient supply, immune response, and metabolism. Particularly, cancer cells exploit activated macropinocytosis to obtain nutrients for supporting proliferation and survival under nutritional stress. Thus, macropinocytosis emerges as an important target for cancer therapy. Furthermore, as activated macropinocytosis constitutively uptakes extracellular fluids into cancer cells, it has been utilized for delivering anti-tumor drugs in cancer therapy. In this review, we systematically addressed progress in cancer therapeutic strategies in both targeting macropinocytosis and utilizing macropinocytosis as an anti-cancer drug delivering tool, including therapeutic applications with macropinocytosis inhibitors; metabolic modulators; methuosis (the macropinocytosis-associated cell death) inducers; and macropinocytosis-mediated anti-cancer drug delivery strategies such as nanoparticles, viral vectors, extracellular vesicles, and targeted conjugates. We conclude that developing targeted macropinocytosis anti-cancer drugs and exploring macropinocytosis-dependent anti-cancer drug delivery systems open new avenues for cancer therapy.
巨吞饮作用是一种非选择性的、不依赖网格蛋白的内吞过程，它通过质膜重塑和随后形成巨吞饮小体，促进细胞外液及其溶解成分（包括蛋白质、脂质和核苷酸）的大量内化。这种进化上保守的细胞过程在营养供应、免疫反应和代谢中发挥着重要作用。特别是，癌细胞利用激活的巨吞饮作用在营养应激下获取营养以支持增殖和存活。因此，巨吞饮作用成为癌症治疗的一个重要靶点。此外，由于激活的巨吞饮作用持续地将细胞外液摄入癌细胞，它已被用于癌症治疗中的抗肿瘤药物递送。在这篇综述中，我们系统地阐述了在靶向巨吞饮作用和利用巨吞饮作用作为抗癌药物递送工具方面癌症治疗策略的进展，包括使用巨吞饮作用抑制剂；代谢调节剂；类凋亡（与巨吞饮作用相关的细胞死亡）诱导剂；以及巨吞饮作用介导的抗癌药物递送策略，如纳米颗粒、病毒载体、细胞外囊泡和靶向偶联物。我们得出结论，开发靶向巨吞饮作用的抗癌药物和探索依赖巨吞饮作用的抗癌药物递送系统为癌症治疗开辟了新途径。
