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Au@Pd nanozyme-mediated catalytic therapy: a novel strategy for targeting tumor microenvironment in cancer treatment.
Luo, Min; Zhao, Fu-Kun; Wang, Yuan-Min; Bian, Jiang.
Afiliación
  • Luo M; The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, Zunyi, Guizhou, 563000, China.
  • Zhao FK; The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, Zunyi, Guizhou, 563000, China.
  • Wang YM; The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, Zunyi, Guizhou, 563000, China.
  • Bian J; Dali University, No.2 Hongsheng Road, Dali Town, Dali City, 671003, Yunnan Province, China. 19707763798@163.com.
J Transl Med ; 22(1): 814, 2024 Sep 02.
Article en En | MEDLINE | ID: mdl-39223625
ABSTRACT

BACKGROUND:

Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations.

METHODS:

In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood.

RESULTS:

Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects.

CONCLUSIONS:

This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paladio / Apoptosis / Nanopartículas del Metal / Microambiente Tumoral / Oro Límite: Animals / Female / Humans Idioma: En Revista: J Transl Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paladio / Apoptosis / Nanopartículas del Metal / Microambiente Tumoral / Oro Límite: Animals / Female / Humans Idioma: En Revista: J Transl Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido