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基于 Fe-HCOF-PEG 的缺氧耐受型光敏剂触发铁死亡并增强基于 ROS 的癌症治疗

Fe-HCOF-PEG as a Hypoxia-Tolerant Photosensitizer to Trigger Ferroptosis and Enhance ROS-Based Cancer Therapy.

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

Center for Clinical Laboratory, General Hospital of the Yangtze River Shipping Wuhan Brain Hospital, Wuhan, Hubei, 430010, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Oct 7;19:10165-10183. doi: 10.2147/IJN.S479848. eCollection 2024.

DOI:10.2147/IJN.S479848
PMID:39399828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11468433/
Abstract

BACKGROUND: The hypoxic tumor microenvironment and single mechanisms severely limit the photodynamic therapy (PDT) efficiency of covalent organic framework (COF) nanoparticles in cancer treatment. PURPOSE: Here, we propose an iron-loaded, hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000)-modified hollow covalent organic framework (HCOF), Fe-HCOF-PEG, for use in hypoxic PDT and ferroptosis therapy owing to its type I and II photodynamic ability and iron nanoparticle loading property. RESULTS: Fe-HCOF-PEG nanoparticles (Fe-HCOFs-PEG) with semiconducting polymers and microporous skeletons allow efficient photophysical properties. Moreover, the iron nanoparticles on Fe-HCOF-PEG caused ferroptosis and further enhanced tumor elimination under normoxic and hypoxic conditions. DSPE-PEG endowed Fe-HCOF-PEG with hydrophilicity, allowing it to circulate and accumulate in organs rich in blood supply, especially tumors. 808 nm NIR activated Fe-HCOF-PEG aggregated in tumors and significantly inhibited tumor growth under hypoxia. CONCLUSION: To our knowledge, Fe-HCOF-PEG is the leading combination of type I/II PDT and ferroptosis. The strong antitumor effects of this nanomaterial suggest prospects for clinical translation as a tumor nanotherapy drug.

摘要

背景：缺氧肿瘤微环境和单一机制严重限制了共价有机骨架（COF）纳米粒子在癌症治疗中的光动力疗法（PDT）效率。

目的：在这里，我们提出了一种负载铁、亲水性 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]（DSPE-PEG2000）修饰的中空共价有机骨架（HCOF），Fe-HCOF-PEG，由于其具有 I 型和 II 型光动力能力和铁纳米粒子负载特性，可用于缺氧 PDT 和铁死亡治疗。

结果：具有半导体聚合物和微孔骨架的 Fe-HCOF-PEG 纳米粒子（Fe-HCOFs-PEG）具有高效的光物理特性。此外，Fe-HCOF-PEG 上的铁纳米颗粒在常氧和缺氧条件下引起铁死亡，并进一步增强肿瘤消除。DSPE-PEG 赋予 Fe-HCOF-PEG 亲水性，使其能够在富含血液供应的器官中循环和积累，特别是肿瘤。808nmNIR 激活的 Fe-HCOF-PEG 在肿瘤中聚集，并在缺氧下显著抑制肿瘤生长。

结论：据我们所知，Fe-HCOF-PEG 是 I/II 型 PDT 和铁死亡的领先结合。这种纳米材料的强大抗肿瘤作用表明其有望作为肿瘤纳米治疗药物进行临床转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/361fda412e38/IJN-19-10165-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/830a5825a0f2/IJN-19-10165-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/38f1590e33d9/IJN-19-10165-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/2a8f1488e321/IJN-19-10165-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/d5dcee1217f8/IJN-19-10165-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/e8c5dd92f95c/IJN-19-10165-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/db186838aa80/IJN-19-10165-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/1d85adf9b18e/IJN-19-10165-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/60d93297d4df/IJN-19-10165-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/361fda412e38/IJN-19-10165-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/830a5825a0f2/IJN-19-10165-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/38f1590e33d9/IJN-19-10165-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/2a8f1488e321/IJN-19-10165-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/d5dcee1217f8/IJN-19-10165-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/e8c5dd92f95c/IJN-19-10165-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/db186838aa80/IJN-19-10165-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/1d85adf9b18e/IJN-19-10165-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/60d93297d4df/IJN-19-10165-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfa/11468433/361fda412e38/IJN-19-10165-g0009.jpg

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引用本文的文献

[1]
Advances in understanding ferroptosis mechanisms and their impact on immune cell regulation and tumour immunotherapy.

Discov Oncol. 2025-2-10

本文引用的文献

[1]
The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions.

Cancer Cell. 2024-4-8

[2]
Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance.

Sci China Life Sci. 2024-1

[3]
Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy.

Nat Commun. 2023-9-2

[4]
Recent progress in covalent organic frameworks for cancer therapy.

Drug Discov Today. 2023-6

[5]
Depriving Tumor Cells of Ways to Metastasize: Ferroptosis Nanotherapy Blocks Both Hematogenous Metastasis and Lymphatic Metastasis.

Nano Lett. 2023-4-26

[6]
Covalent Organic Frameworks: Recent Progress in Biomedical Applications.

ACS Nano. 2023-2-14

[7]
A self-assembly nano-prodrug for triple-negative breast cancer combined treatment by ferroptosis therapy and chemotherapy.

Acta Biomater. 2023-3-15

[8]
Overcoming cancer chemotherapy resistance by the induction of ferroptosis.

Drug Resist Updat. 2023-1

[9]
Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor-Specific and Ferroptosis-Augmented Sonodynamic Therapy.

Adv Sci (Weinh). 2023-2

[10]
Biomimetic photosensitizer nanocrystals trigger enhanced ferroptosis for improving cancer treatment.

J Control Release. 2022-12

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