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CD44 and αV-integrins dual-targeting bimetallic nanozymes for lung adenocarcinoma therapy via NIR-enhanced ferroptosis/apoptosis

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资源类型：
Pubmed体系：
作者：
He Jingchuan[1,2] * ; Li Tingting[1,3] * ; Pan Xiaoqin[1] * ; Deng Zhihua[1,4] ; Huang Jifu[1] ; Mo Xiaocheng[1,5] ; Shen Xiaoju[1,5] ; Qin Xiumei[1] ; Yang Xingye[6] ; Gao Ming[7] ; Yang Jie[1,8,9] ;
机构： [1]Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China [2]Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, 530021, China [3]Department of Pharmacy, The Second Affiliated Hospital of North Sichuan Medical College, Nanchong, 637100, China [4]Department of Gastrointestinal Medicine, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, China [5]Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China [6]Department of Pharmaceutics, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China [7]Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China [8]Guangxi Key Laboratory of Drug Basic Research for Prevention and Treatment of Geriatric Diseases, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China [9]The Laboratory of Toxicology of Traditional Chinese Medicine, Level III Laboratory of National Administration of Traditional Chinese Medicine, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China
出处：
DOI： 10.1016/j.biomaterials.2025.123407
ISSN：

关键词： CD44 and αV-integrin receptors Dual-targeting bimetallic nanozymes NIR Ferroptosis and apoptosis Lung cancer therapy

摘要：
Combination therapy is a promising strategy for lung adenocarcinoma (LUAD), due to the advantages of overcoming drug resistance, side effects, and tumor heterogeneity. Herein, we report a novel dual-targeting bimetallic nanozyme (MH-iRGD) consisting of nanosized manganese ferrite (MF) after encapsulating with dopamine and methacrylic anhydride to modify hyaluronic acid, followed by integrin receptor targeting peptide (HS-PEG3400-iRGD) modification for LUAD targeted therapy. Our study confirmed that MH-iRGD combined with near-infrared irradiation (NIR) possessed dramatic photothermal effects and reactive oxygen species (ROS) production and GSH depletion abilities. Importantly, MH-iRGD possessed dual-targeting capacities for LUAD cells overexpressed CD44 and αV-integrin receptors owing to hyaluronic acid coating and iRGD modification. Inhibitors of CD44 and integrins could impair the uptake of MH-iRGD in LUAD cells. Moreover, MH-iRGD + NIR displayed excellent anti-LUAD effects as a result of the production of intracellular ROS, consumption of glutathione (GSH) and mitochondrial dysfunction. Mechanistically, NIR robustly strengthened MH-iRGD-induced ferroptosis and apoptosis by down-regulating SLC7A11, GPX4, Bcl-2 levels while up-regulating Bax level. Specifically, ferroptosis and apoptosis were increased while the LUAD progression was inhibited after intravenous injection of MH-iRGD + NIR in xenograft mouse models. Taken together, our results indicate that MH-iRGD + NIR serves as a promising targeted therapy for LUAD, which broadens the applications of highly active dual-targeting bimetallic nanozymes.Copyright © 2025 Elsevier Ltd. All rights reserved.

基金：
This research was financially supported by the National Natural Science Foundation of China (No. 82374093), Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation under Grant (No. 2024GXNSFBA010027), National Natural Science Foundation of China (No. 82160698), National Natural Science Foundation of China (No. 82160430), Science and Technology Planning Project of Nanning Qingxiu District (No. 2021013), Guangxi Medical University Training Program for Distinguished Young Scholars, Guangxi First-class Discipline Project for Pharmaceutical Sciences (No. GXFCDP- PS-2018), Guangxi Medical University college students innovation and entrepreneurship training program (No. S202310598125).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 医学
小类 | 1 区 工程：生物医学 1 区 材料科学：生物材料
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 工程：生物医学 1 区 材料科学：生物材料
第一作者：
第一作者机构： [1]Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China [2]Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, 530021, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China [8]Guangxi Key Laboratory of Drug Basic Research for Prevention and Treatment of Geriatric Diseases, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China [9]The Laboratory of Toxicology of Traditional Chinese Medicine, Level III Laboratory of National Administration of Traditional Chinese Medicine, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China
推荐引用方式(GB/T 7714)：
He Jingchuan,Li Tingting,Pan Xiaoqin,et al.CD44 and αV-integrins dual-targeting bimetallic nanozymes for lung adenocarcinoma therapy via NIR-enhanced ferroptosis/apoptosis[J].Biomaterials.2025,323:123407.doi:10.1016/j.biomaterials.2025.123407.
APA：
He Jingchuan,Li Tingting,Pan Xiaoqin,Deng Zhihua,Huang Jifu...&Yang Jie.(2025).CD44 and αV-integrins dual-targeting bimetallic nanozymes for lung adenocarcinoma therapy via NIR-enhanced ferroptosis/apoptosis.Biomaterials,323,
MLA：
He Jingchuan,et al."CD44 and αV-integrins dual-targeting bimetallic nanozymes for lung adenocarcinoma therapy via NIR-enhanced ferroptosis/apoptosis".Biomaterials 323.(2025):123407

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