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化学进展 2023, Vol. 35 Issue (11): 1655-1673 DOI: 10.7536/PC230330 前一篇   后一篇

• 综述 •

基于纳米材料介导的自噬治疗癌症

金卫涛, 杨婷, 贾吉美, 周晓斐*()   

  1. 河北农业大学 保定 071000
  • 收稿日期:2023-03-30 修回日期:2023-05-21 出版日期:2023-11-24 发布日期:2023-09-11
  • 通讯作者: 周晓斐
  • 作者简介:

    周晓斐 女,副教授,硕士生导师。2019年在山东大学获博士学位,2019年至今在河北农业大学任教。主要从事环境污染物的人体健康效应、机理研究及靶向药物研究工作。在 Science of the Total Environment、ACS Applied Materials & Interfaces、Nanoscale、Journal of Environmental Sciences、Frontiers in Bioengineering and Biotechnology、RSC Advances等期刊作为第一作者或通讯作者发表SCI论文多篇。

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Nanomaterials-Mediated Autophagy-Based Cancer Treatment

Jin Weitao, Yang Ting, Jia Jimei, Zhou Xiaofei()   

  1. Hebei Agriculture University,Baoding 071000, China
  • Received:2023-03-30 Revised:2023-05-21 Online:2023-11-24 Published:2023-09-11
  • Contact: Zhou Xiaofei

随着纳米技术的快速发展,纳米材料在癌症治疗领域得到了广泛的应用。众所周知,自噬作为一个维持细胞稳态的过程,在癌症发展中发挥着促生存和促死亡的双重作用。癌细胞中的自噬水平远高于正常细胞,从而导致各种治疗策略效果不理想。通过扰动自噬协同治疗癌症已经成为了一种可行的方案,但是传统自噬扰动剂如氯喹等可能导致某些其他的副作用。此外,已有研究证明了纳米材料可以作为一种新型的自噬扰动剂,但是纳米材料干扰自噬的机制需要更加深入的了解。本文综述了癌症与自噬的双重关系,并重点介绍了多种纳米材料通过扰动自噬诱导癌细胞死亡或凋亡,或者通过扰动自噬增强癌细胞对传统癌症治疗的敏感性,以及它们调控自噬的机制。

关键词： 纳米材料, 癌症, 自噬, 耐药性

With the rapid development of nanotechnology, nanomaterials have been widely used in the field of cancer treatment. It is well known that autophagy, as a process that maintains cellular homeostasis, plays a dual role in promoting survival and death in cancer development. The level of autophagy in cancer cells is significantly higher than that in normal cells, resulting in various treatment strategies being ineffective. Synergistic treatment of cancer by perturbing autophagy has become a viable option, but traditional autophagy perturbing agents such as chloroquine may lead to certain other side effects. In addition, it has been demonstrated that nanomaterials can be used as a novel autophagy perturber, but the mechanism by which nanomaterials interfere with autophagy needs to be more deeply understood. This review provides an overview of the dual relationship between cancer and autophagy, and highlights the mechanisms by which various nanomaterials induce cancer cell death or apoptosis by perturbing autophagy, or enhance the sensitivity of cancer cells to conventional cancer therapy by perturbing autophagy, and the mechanisms by which they modulate autophagy.

Contents

1 Introduction

2 Cancer and autophagy

2.1 Autophagy inhibits the occurrence of cancer

2.2 Autophagy promotes cancer development

3 Effect of nanomaterials on autophagy

4 Nanomaterials treat cancer by perturbing autophagy

4.1 Metallic nanomaterials

4.2 Oxide nanomaterials

4.3 Carbon based nanomaterials

4.4 Other Nanomaterials

5 Mechanisms of autophagy perturbed by nanomaterials

5.1 Oxidation stress

5.2 Perturbation of autophagy-related signaling pathways

5.3 Lysosomal dysfunction

6 Conclusion

Key words: nanomaterials, cancer, autophagy, drug resistance
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图1 纳米材料通过扰动自噬治疗癌症示意图
Fig.1 Schematic diagram of nanomaterials for cancer treatment by perturbing autophagy
表1 纳米材料通过调控自噬治疗癌症
Table 1 Nanomaterials treat cancer by regulating autophagy
NMs Size (nm) shape or
dispersity		 Coating Drug or therapies Model cells Mechanism Autophagy Effect ref
Au NPs 20 sphere PEG immunotherapy Hepa1-6 cells;
RAW 264.7 cells		 Lysosome alkalization; membrane permeabilization Inhibition Increased sensitivity 79
Au NPs 30~60 Peanut Bare — SKOV-3 cell ROS upregulation Inhibition Apoptosis 78
Ag NPs 66.92 sphere Bare — PC-3 cell lysosome injury; cell hypoxia Inhibition Cell death 93
Fe3O4-Au NPs 15~25 sphere — DOX HepG2 cells Enhancing autophagosome formation Induction Reduce drug resistance 80
Ag NPs 59 sphere Bare — HT-29 cells JNK activation and
eIF2α phosphorylation		 Induction Apoptosis 97
Fe@Au
NPs		 — core-shell structure — — OECM1 cell Mitochondria damage Inhibition Cell death 73
Ag NPs 26.5 sphere PVP — HeLa cell PtdIns3K-dependent Induction Ehances the anticancer activity 90
Fe3O4 NPs 36 sphere PEG PTX U251 cell ROS upregulation Induction Reduce drug resistance 98
Ag NPs 13 sphere — — A549 cell ROS upregulation Induction Apoptosis 83
Ag NPs 8 sphere protein Cisplatin OS cell; HCC cell MAPK pathways Induction Reduce drug resistance 89
Fe2O3 NPs 10 sphere DMSA — SK-Hep-1 cell ROS upregulation;
MAPK pathways		 Induction Cell death 99
CuO NPs 10 sphere — — MCF7 cell ROS dependent Induction Growth inhibition 100
ZnO NPs 21 — — Sorafenib Huh 7 cell Promoting p53 Gene Induction Apoptosis 101
ZnO NPs 63 — — — MCF7 cell — Inhibition Apoptosis 102
SiO2 NPs 86 sphere HCT-116 cells ER stress Induction Cell survival 103
Ag NPs 15.38 sphere PVP Radiotherapy U251 cells ROS upregulation Induction Increased sensitivity 88
IONPs 37 — PEG — U251 cells Beclin 1/ATG 5 pathways Induction Ferroptosis 30
Gd2O3 NPs — — — Cisplatin HeLa cells — Inhibition Reduce drug resistance 104
SiO2 NPs 125 sphere — Propranolol HemSCs cells ER stress Induction Cell death 105
ZnO NPs 20 — — — SKOV3 cells ROS upregulation Induction Apoptosis 106
SiO2 NPs 198 sphere PDA; PEG DOX MCF7 cells AKT-mTOR-p70S6K pathway Induction Cell death 40
ND 191 — — Hypoxia HeLa cells; MCF7 cells — Inhibition Apoptosis 107
ZnO NPs — — — Cisplatin SGC7901 cells;BGC823 cells — Inhibition Reduce drug resistance 108
GO 450 sheet DMSO Cisplatin Skov-3 cells — Induction Cell death 109
DWCNTs — Tube — — DHD/K12/Trb cell line Intracellular acidification Induction Cell death 110
Se NPs 70 Amorphous solid — Astragalus Polysaccharides MCF7 cells ROS upregulation and Mitochondria damage Inhibition Apoptosis 111
BPQDs 140 Monodisperse Platelet membrane Hederagenin MCF7 cells; RAW 264.7 cells ROS upregulation and Mitochondria damage Induction Apoptosis 112
Co3O4 NPs 200 sphere — Photothermal therapy U-87 MG cells Llysosomal function damage Blockage of autophagic flux Cell death 113
图2 脱铁蛋白包裹铜多吡啶复合物的纳米颗粒诱导多重耐药的结直肠癌细胞自噬依赖性凋亡示意图[97]
Fig.2 Schematic diagram of autophagy-dependent apoptosis of multi-drug resistant colorectal cancer cells induced by nanoparticles of apoferritin -coated copper polypyridine complex[97]. Copyright © 2022, American Chemical Society
图3 纳米材料影响自噬相关信号通路示意图[44]
Fig.3 Schematic diagram of signal pathways related to the influence of nanomaterials on autophagy[44]. Copyright © 2014, American Chemical Society
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