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Inhalable biomimetic polyunsaturated fatty acid-based nanoreactors for peroxynitrite-augmented ferroptosis potentiate radiotherapy in lung cancer.

作者信息

Chen Yiting, Huang Xueli, Hu Ruining, Lu Enhao, Luo Kuankuan, Yan Xin, Zhang Zhiwen, Ma Yan, Zhang Minghe, Sha Xianyi

机构信息

Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Lane 826, Zhangheng Road, Shanghai, 201203, China.

Department of Pharmacy, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China.

出版信息

J Nanobiotechnology. 2025 May 8;23(1):338. doi: 10.1186/s12951-025-03409-8.


DOI:10.1186/s12951-025-03409-8
PMID:40340938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12060495/
Abstract

The limited efficacy and poor tumor accumulation remain crucial challenges for radiotherapy against lung cancer. To address these limitations, we rationally developed a polyunsaturated fatty acid (PUFA)-based nanoreactor (DHA-N@M) camouflaged with macrophage cell membrane to improve tumoral distribution and achieve peroxynitrite-augment ferroptosis for enhanced radiotherapy against lung cancer. After nebulization, the nanoreactors exhibited superior pulmonary accumulation in orthotopic lung cancer-bearing mice, with 70-fold higher than intravenously injected nanoreactors at 12 h post-administration, and distributed deeply in the tumors. DHA-N@M selectively released nitric oxide (NO) in glutathione (GSH)-enriched tumor cells, with consumption of GSH and subsequent inactivation of glutathione peroxidase 4 (GPX4). Under radiation, NO reacted with radiotherapy-induced reactive oxygen species (ROS) to generate peroxynitrite (ONOO), resulting in redox homeostasis disruption. Combined with docosahexaenoic acid (DHA)-induced lipid metabolism disruption, overwhelming ferroptosis was induced both in vitro and in vivo. Notably, DHA-N@M mediated ferroptosis-radiotherapy significantly suppressed tumor growth with a 93.91% inhibition in orthotopic lung cancer models. Therefore, this design provides a nebulized ferroptosis-radiotherapy strategy for lung cancer.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/31c596fa40c0/12951_2025_3409_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/4fd39212f409/12951_2025_3409_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/da94bb0b98b2/12951_2025_3409_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/9d090634bae8/12951_2025_3409_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/8d0e826d752a/12951_2025_3409_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/2b6e517124db/12951_2025_3409_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/c66ebd3b9b3d/12951_2025_3409_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/31c596fa40c0/12951_2025_3409_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/4fd39212f409/12951_2025_3409_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/da94bb0b98b2/12951_2025_3409_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/9d090634bae8/12951_2025_3409_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/8d0e826d752a/12951_2025_3409_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/2b6e517124db/12951_2025_3409_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/c66ebd3b9b3d/12951_2025_3409_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3acb/12060495/31c596fa40c0/12951_2025_3409_Fig7_HTML.jpg

相似文献

[1]
Inhalable biomimetic polyunsaturated fatty acid-based nanoreactors for peroxynitrite-augmented ferroptosis potentiate radiotherapy in lung cancer.

J Nanobiotechnology. 2025-5-8

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

CA Cancer J Clin. 2024

[2]
Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity.

Nat Nanotechnol. 2024-4

[3]
Biomimetic Macrophage Membrane-Camouflaged Nanoparticles Induce Ferroptosis by Promoting Mitochondrial Damage in Glioblastoma.

ACS Nano. 2023-12-12

[4]
Stimuli-Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy.

Small Methods. 2024-1

[5]
Engineered Extracellular Vesicle-Delivered CRISPR/Cas9 for Radiotherapy Sensitization of Glioblastoma.

ACS Nano. 2023-9-12

[6]
Biomineralized RuO Nanozyme with Multi-Enzyme Activity for Ultrasound-Triggered Peroxynitrite-Boosted Ferroptosis.

Small. 2023-11

[7]
Tumor-Generated Reactive Oxygen Species Storm for High-Performance Ferroptosis Therapy.

ACS Nano. 2023-6-27

[8]
Lipid-Based Inhalable Micro- and Nanocarriers of Active Agents for Treating Non-Small-Cell Lung Cancer.

Pharmaceutics. 2023-5-10

[9]
Retinol Saturase Mediates Retinoid Metabolism to Impair a Ferroptosis Defense System in Cancer Cells.

Cancer Res. 2023-7-14

[10]
X-ray-Induced Release of Nitric Oxide from Hafnium-Based Nanoradiosensitizers for Enhanced Radio-Immunotherapy.

Adv Mater. 2023-7

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