纳米材料用于铁死亡联合治疗的研究进展

doi:10.16085/j.issn.1000-6613.2022-1595

摘要/Abstract

摘要：

铁死亡作为一种新发现的调节性细胞死亡形式已成为新型的肿瘤治疗策略，然而复杂的肿瘤微环境及肿瘤部位特殊的病理微环境严重限制了铁死亡的治疗效果。将铁死亡与传统的抗肿瘤治疗方式结合，能提高治疗效率并减少毒副作用。为实现药物在肿瘤部位富集效果并发挥协同治疗效果，基于纳米材料的药物递送体系在抗肿瘤领域显示出广阔的临床应用前景和发展价值。本文首先介绍了不同种类纳米材料（铁基纳米材料及非铁基纳米材料）用于铁死亡协同肿瘤治疗的相关进展，归纳了铁死亡与多种治疗方法（包括化学治疗、光热治疗、光/声动力治疗、其他治疗方式等）协同治疗的相关研究；最后阐明了铁死亡协同肿瘤治疗的挑战，并指出确认铁死亡的具体抗癌机制、开发多功能纳米材料并探索高效协同治疗手段将是未来的研究方向。

关键词: 纳米材料, 药物, 铁死亡, 自由基, 抗肿瘤

Abstract:

Ferroptosis, a programmed cell death modality, has been recognized as one of the exceptional cancer therapeutic strategies. However, the complexity of anatomical and physiological features of tumor microenvironment may weaken the ferroptosis effects for cancer treatment. Fortunately, the combination of ferroptosis with traditional therapeutics provides an easy way of improving the therapeutic efficiency and reducing toxic side effects due to lesser dosages of multiple drugs. Nanomaterials-based drug delivery systems have served as potential anticancer drug agents in clinical translation, which can achieve the tumor-targeted delivery of various practical molecules and improve therapeutic efficiency based on synergistic strategies. In this review, we systematically summarized various novel nanoplatforms (iron-based nanomaterials and nor-iron nanomaterials) for ferroptosis-based combination therapeutics towards highly effective cancer therapy. Then, we provided a brief emphasis on the combination of ferroptosis with multiple strategies, including chemotherapy, photothermal therapy, photo/sonodynamic therapy, and other therapeutics. Finally, we presented various challenges towards developing ferroptosis-based therapeutic strategies, and we believed that the deeper understanding of ferroptosis, the development of multifunctional nanomaterials and the exploration of ferroptosis-based combination therapies would be focus in future.

Key words: nanomaterials, pharmaceuticals, ferroptosis, radical, anticancer

中图分类号:

徐沛瑶, 陈标奇, KANKALA Ranjith Kumar, 王士斌, 陈爱政. 纳米材料用于铁死亡联合治疗的研究进展[J]. 化工进展, 2023, 42(7): 3684-3694.

XU Peiyao, CHEN Biaoqi, KANKALA Ranjith Kumar, WANG Shibin, CHEN Aizheng. Research progress of nanomaterials for synergistic ferroptosis anticancer therapy[J]. Chemical Industry and Engineering Progress, 2023, 42(7): 3684-3694.

图/表 7

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纳米载体名称	协同药物	肿瘤细胞类型	联合治疗方式	参考文献
锰掺杂四氧化三铁纳米颗粒负载阿霉素	阿霉素	肝癌细胞HepG2	化学治疗	[16]
聚多巴胺-四氧化三铁纳米颗粒负载10-羟基喜树碱	10-羟基喜树碱	食管癌细胞EC1及EC109	化学治疗	[22]
四氧化三铁/氧化钆纳米颗粒负载顺铂	顺铂	前列腺癌细胞PC-3	化学治疗	[18]
聚多肽包裹的四氧化三铁纳米颗粒及顺铂	顺铂	脑胶质瘤细胞U87 MG	化学治疗	[23]
铁基MOF修饰的四氧化三铁纳米颗粒负载IR780	IR780	乳腺癌细胞4T1	光热治疗	[17]
多孔聚多巴胺负载超顺磁性氧化铁纳米颗粒及索拉非尼	索拉非尼	结肠癌细胞HCT116	光热治疗	[24]
硒化铋纳米片负载四氧化三铁纳米颗粒及金纳米颗粒	金纳米颗粒	乳腺癌细胞4T1	光热治疗	[25]
卟啉接枝脂质体包裹四氧化三铁纳米颗粒	卟啉	结肠癌细胞HT-29	光动力治疗	[19]
聚乳酸-羟基乙酸包裹四氧化三铁纳米颗粒及Ce6	Ce6	乳腺癌细胞4T1	光动力治疗	[26]
细胞膜包裹四氧化三铁纳米颗粒及Ce6	Ce6	神经胶质瘤细胞C6	声动力治疗	[27]
细胞膜包裹四氧化三铁纳米颗粒及siPD-L1	siPD-L1	耐替莫唑胺小胶质瘤细胞GL261/TR	免疫治疗	[21]
红细胞膜包裹的四氧化三铁纳米颗粒及柳氮磺胺吡啶	柳氮磺胺吡啶	乳腺癌细胞4T1	免疫治疗	[28]
铁离子多酚网络包覆的四氧化三铁纳米颗粒负载葡萄糖氧化酶及阿霉素前药	葡萄糖氧化酶、阿霉素前药	耐阿霉素乳腺癌细胞MCF-7/Adr	化学治疗、饥饿治疗	[29]
明胶包裹四氧化三铁纳米颗粒及阿霉素	阿霉素	肝癌细胞LM3	化学治疗、微波热疗	[30]

纳米载体名称	协同药物	肿瘤细胞类型	联合治疗方式	参考文献
锰掺杂四氧化三铁纳米颗粒负载阿霉素	阿霉素	肝癌细胞HepG2	化学治疗	[16]
聚多巴胺-四氧化三铁纳米颗粒负载10-羟基喜树碱	10-羟基喜树碱	食管癌细胞EC1及EC109	化学治疗	[22]
四氧化三铁/氧化钆纳米颗粒负载顺铂	顺铂	前列腺癌细胞PC-3	化学治疗	[18]
聚多肽包裹的四氧化三铁纳米颗粒及顺铂	顺铂	脑胶质瘤细胞U87 MG	化学治疗	[23]
铁基MOF修饰的四氧化三铁纳米颗粒负载IR780	IR780	乳腺癌细胞4T1	光热治疗	[17]
多孔聚多巴胺负载超顺磁性氧化铁纳米颗粒及索拉非尼	索拉非尼	结肠癌细胞HCT116	光热治疗	[24]
硒化铋纳米片负载四氧化三铁纳米颗粒及金纳米颗粒	金纳米颗粒	乳腺癌细胞4T1	光热治疗	[25]
卟啉接枝脂质体包裹四氧化三铁纳米颗粒	卟啉	结肠癌细胞HT-29	光动力治疗	[19]
聚乳酸-羟基乙酸包裹四氧化三铁纳米颗粒及Ce6	Ce6	乳腺癌细胞4T1	光动力治疗	[26]
细胞膜包裹四氧化三铁纳米颗粒及Ce6	Ce6	神经胶质瘤细胞C6	声动力治疗	[27]
细胞膜包裹四氧化三铁纳米颗粒及siPD-L1	siPD-L1	耐替莫唑胺小胶质瘤细胞GL261/TR	免疫治疗	[21]
红细胞膜包裹的四氧化三铁纳米颗粒及柳氮磺胺吡啶	柳氮磺胺吡啶	乳腺癌细胞4T1	免疫治疗	[28]
铁离子多酚网络包覆的四氧化三铁纳米颗粒负载葡萄糖氧化酶及阿霉素前药	葡萄糖氧化酶、阿霉素前药	耐阿霉素乳腺癌细胞MCF-7/Adr	化学治疗、饥饿治疗	[29]
明胶包裹四氧化三铁纳米颗粒及阿霉素	阿霉素	肝癌细胞LM3	化学治疗、微波热疗	[30]

治疗方式	优势	缺点	治疗方式联合铁死亡治疗的特点
化学治疗	普适性高、可操作性强、临床数据完善	全身毒副作用强，易引发耐药	通过降低化疗药物药量以减轻毒副作用；铁死亡可逆转多药耐药性以提高化学治疗的敏感性
光热治疗	低创、治疗时间短、毒副作用小	难以清除深层肿瘤，低温治疗效果不佳，高温治疗导致正常组织损伤	光热治疗可促进芬顿反应的速率进而促进铁死亡；铁死亡可抑制HSP蛋白的表达，实现低温光热治疗
光动力/声动力治疗	低创、高效、毒副作用小	难以清除深层肿瘤，肿瘤乏氧微环境导致疗效不佳	铁死亡可通过芬顿反应产生氧气，减轻肿瘤乏氧，提高光动力/声动力治疗效果

治疗方式	优势	缺点	治疗方式联合铁死亡治疗的特点
化学治疗	普适性高、可操作性强、临床数据完善	全身毒副作用强，易引发耐药	通过降低化疗药物药量以减轻毒副作用；铁死亡可逆转多药耐药性以提高化学治疗的敏感性
光热治疗	低创、治疗时间短、毒副作用小	难以清除深层肿瘤，低温治疗效果不佳，高温治疗导致正常组织损伤	光热治疗可促进芬顿反应的速率进而促进铁死亡；铁死亡可抑制HSP蛋白的表达，实现低温光热治疗
光动力/声动力治疗	低创、高效、毒副作用小	难以清除深层肿瘤，肿瘤乏氧微环境导致疗效不佳	铁死亡可通过芬顿反应产生氧气，减轻肿瘤乏氧，提高光动力/声动力治疗效果

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