Liu Yunmeng, Wang Yaxin, Zhang Jincheng, Peng Qikai, Wang Xingdong, Xiao Xiyue, Shi Kai
College of Pharmacy, Nankai University, Tianjin 300350, China.
Acta Pharm Sin B. 2024 Jun;14(6):2447-2474. doi: 10.1016/j.apsb.2024.03.019. Epub 2024 Mar 18.
The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.
当前癌症治疗的临床疗效欠佳，迫切需要将新靶点与传统疗法相结合。自噬是一种高度保守的自我降解过程，作为一种新兴的癌症治疗靶点已受到广泛关注。随着纳米医学的迅速发展，纳米材料因其无与伦比的递送性能而被广泛应用于癌症治疗。因此，考虑到自噬与纳米技术相结合在癌症治疗中的潜在益处，我们概述了基于自噬的纳米疗法的最新进展。基于与自噬和纳米疗法相关的简要背景及其对肿瘤进展的影响，论证了基于自噬的纳米疗法用于癌症治疗的可行性。此外，从细胞信号通路的角度对为调节自噬而开发的新兴纳米疗法进行了综述，包括对雷帕霉素靶蛋白（mTOR）通路、自噬相关蛋白（ATG）及其复合物表达、活性氧（ROS）和线粒体自噬的调节，对自噬体-溶酶体融合的干扰以及对缺氧介导的自噬的抑制。此外，还介绍了纳米自噬调节与化疗、光疗和免疫疗法相结合的联合疗法。最后，展望了基于自噬的纳米疗法在高效癌症治疗方面的前景与挑战。
