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纳米治疗学在自噬中的应用:癌症治疗的范式转变。

Nanotherapeutics in autophagy: a paradigm shift in cancer treatment.

机构信息

Department of Pharmaceutical Eng. & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, UP, India.

出版信息

Drug Deliv Transl Res. 2022 Nov;12(11):2589-2612. doi: 10.1007/s13346-022-01125-6. Epub 2022 Feb 11.

Abstract

Autophagy is a catabolic process in which an organism responds to its nutrient or metabolic emergencies. It involves the degradation of cytoplasmic proteins and organelles by forming double-membrane vesicles called "autophagosomes." They sequester cargoes, leading them to degradation in the lysosomes. Although autophagy acts as a protective mechanism for maintaining homeostasis through cellular recycling, it is ostensibly a cause of certain cancers, but a cure for others. In other words, insufficient autophagy, due to genetic or cellular dysfunctions, can lead to tumorigenesis. However, many autophagy modulators are developed for cancer therapy. Diverse nanoparticles have been documented to induce autophagy. Also, the highly stable nanoparticles show blockage to autophagic flux. In this review, we revealed a general mechanism by which autophagy can be induced or blocked via nanoparticles as well as several studies recently performed to prove the stated fact. In addition, we have also elucidated the paradoxical roles of autophagy in cancer and how their differential role at different stages of various cancers can affect its treatment outcomes. And finally, we summarize the breakthroughs in cancer disease treatments by using metallic, polymeric, and liposomal nanoparticles as potent autophagy modulators.

摘要

自噬是一种分解代谢过程,生物体在面临营养或代谢紧急情况时会启动该过程。该过程涉及通过形成双层膜囊泡(称为“自噬体”)来降解细胞质蛋白和细胞器。自噬体将货物隔离,导致它们在溶酶体中降解。尽管自噬作为一种通过细胞循环来维持体内平衡的保护机制,但它显然是某些癌症的病因,但也是另一些癌症的治疗方法。换句话说,由于遗传或细胞功能障碍导致的自噬不足可能会导致肿瘤发生。然而,已经开发出许多自噬调节剂用于癌症治疗。有文献记载,多种纳米颗粒可诱导自噬。此外,高度稳定的纳米颗粒会阻止自噬通量。在这篇综述中,我们揭示了纳米颗粒可通过通用机制诱导或阻断自噬,以及最近进行的一些研究来证明这一事实。此外,我们还阐明了自噬在癌症中的矛盾作用,以及自噬在各种癌症不同阶段的不同作用如何影响其治疗效果。最后,我们总结了使用金属、聚合和脂质体纳米颗粒作为有效的自噬调节剂来治疗癌症疾病的突破。

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