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涂覆有金属-多酚网络的介孔聚多巴胺纳米颗粒用于肺癌的去甲基化治疗

Mesoporous polydopamine nanoparticles coated with metal-polyphenol networks for demethylation therapy of lung cancer.

作者信息

Wang Jingsi, Deng Xufeng, Li Manyuan, Liu Xiaobing, Liu Quanxing

机构信息

Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.

Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing, China.

出版信息

Med Oncol. 2025 Apr 1;42(5):147. doi: 10.1007/s12032-025-02681-w.

Abstract

The treatment of lung cancer with azacitidine (AZA) is urgently in need of a novel delivery material due to its limitations, including a short half-life, high cytotoxicity, and poor tumor targeting. To overcome these limitations, the coordination of Gallic acid-catechin-gallate with Fe and its encapsulation on the surface of mPDA loaded with AZA (mA@EF) was prepared. mA@EF exhibited a uniform distribution of regular spherical particles with good stability and drug release properties. In cell experiments, mA@EF effectively inhibited cell viability, promoted cellular uptake, and downregulated the expression of DNA methyltransferases. Moreover, mA@EF demonstrated good biosafety. In animal experiments, mA@EF showed strong tumor-targeting and retention activity, and significantly inhibited the growth of tumor. This discovery provided a feasible dosing regimen for AZA treatment in lung cancer patients.

摘要

由于阿扎胞苷(AZA)治疗肺癌存在局限性,包括半衰期短、细胞毒性高和肿瘤靶向性差等,因此迫切需要一种新型递送材料。为了克服这些局限性,制备了没食子酸 - 儿茶素 - 没食子酸酯与铁的配位化合物,并将其包裹在负载有AZA的介孔聚多巴胺(mPDA)表面(mA@EF)。mA@EF呈现出规则球形颗粒的均匀分布,具有良好的稳定性和药物释放特性。在细胞实验中,mA@EF有效抑制细胞活力,促进细胞摄取,并下调DNA甲基转移酶的表达。此外,mA@EF表现出良好的生物安全性。在动物实验中,mA@EF显示出强大的肿瘤靶向和滞留活性,并显著抑制肿瘤生长。这一发现为肺癌患者的AZA治疗提供了一种可行的给药方案。

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