2. Academic Validation
  3. CD44 and αV-integrins dual-targeting bimetallic nanozymes for lung adenocarcinoma therapy via NIR-enhanced ferroptosis/apoptosis

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

  • Biomaterials. 2025 Dec:323:123407. doi: 10.1016/j.biomaterials.2025.123407.
Jingchuan He 1,  Tingting Li 2,  Xiaoqin Pan 3,  Zhihua Deng 4,  Jifu Huang 3,  Xiaocheng Mo 5,  Xiaoju Shen 5,  Xiumei Qin 3,  Xingye Yang 6,  Ming Gao 7,  Jie Yang 8
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, 530021, China.
  • 2 Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Department of Pharmacy, The Second Affiliated Hospital of North Sichuan Medical College, Nanchong, 637100, China.
  • 3 Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China.
  • 4 Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Department of Gastrointestinal Medicine, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, China.
  • 5 Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China; 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. Electronic address: gaoming1983125@hotmail.com.
  • 8 Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Drug Basic Research for Prevention and Treatment of Geriatric Diseases, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China; 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. Electronic address: jieyang2016@gxmu.edu.cn.
PMID: 40403445 DOI: 10.1016/j.biomaterials.2025.123407
Abstract

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.

Keywords

CD44 and αV-integrin receptors; Dual-targeting bimetallic nanozymes; Ferroptosis and apoptosis; Lung cancer therapy; NIR.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100506
    99.43%, Integrin Receptor Antagonist