Chen Jian-Li, Wu Xuan, Yin Dan, Jia Xiao-Hui, Chen Xu, Gu Ze-Yun, Zhu Xiao-Ming
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China.
Pharmacol Ther. 2023 Sep;249:108485. doi: 10.1016/j.pharmthera.2023.108485. Epub 2023 Jul 3.
Autophagy is a conserved process in which the cytosolic materials are degraded and eventually recycled for cellular metabolism to maintain homeostasis. The dichotomous role of autophagy in pathogenesis is complicated. Accumulating reports have suggested that cytoprotective autophagy is responsible for tumor growth and progression. Autophagy inhibitors, such as chloroquine (CQ) and hydroxychloroquine (HCQ), are promising for treating malignancies or overcoming drug resistance in chemotherapy. With the rapid development of nanotechnology, nanomaterials also show autophagy-inhibitory effects or are reported as the carriers delivering autophagy inhibitors. In this review, we summarize the small-molecule compounds and nanomaterials inhibiting autophagic flux as well as the mechanisms involved. The nanocarrier-based drug delivery systems for autophagy inhibitors and their distinct advantages are also described. The progress of autophagy inhibitors for clinical applications is finally introduced, and their future perspectives are discussed.
自噬是一个保守的过程，在此过程中，胞质物质被降解，最终被循环用于细胞代谢以维持体内平衡。自噬在发病机制中的双重作用很复杂。越来越多的报道表明，细胞保护性自噬与肿瘤生长和进展有关。自噬抑制剂，如氯喹（CQ）和羟氯喹（HCQ），有望用于治疗恶性肿瘤或克服化疗中的耐药性。随着纳米技术的快速发展，纳米材料也显示出自噬抑制作用，或被报道为递送自噬抑制剂的载体。在这篇综述中，我们总结了抑制自噬流的小分子化合物和纳米材料及其相关机制。还描述了基于纳米载体的自噬抑制剂药物递送系统及其独特优势。最后介绍了自噬抑制剂在临床应用中的进展，并讨论了它们的未来前景。
