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负载经表面工程处理的纳米颗粒的可植入微针,用于高效根除三阴性乳腺癌干细胞

Implantable Microneedles Loaded with Nanoparticles Surface Engineered for Efficient Eradication of Triple-Negative Breast Cancer Stem Cells.

作者信息

Zhang Weinan, Jiang Yechun, Liu Litao, Shen Hui, Huang Xianyu, Zheng Wang, Chu Zhaoyou, Wang Wanni, Guo Yanchuan, Qian Haisheng

机构信息

School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, P. R. China.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

出版信息

Nano Lett. 2025 Feb 5;25(5):2041-2051. doi: 10.1021/acs.nanolett.4c06052. Epub 2025 Jan 21.

Abstract

Eliminating cancer stem cells (CSCs) is essential for the effective treatment of triple-negative breast cancer (TNBC). This study synthesized Au@cerium-zinc composite core@shell nanoparticles (Au@Zn/CeO) that were subsequently conjugated with () to create the engineered bacterium AZCE, which was then combined with microneedle carriers and freeze-dried to obtain AZCE-MN. Upon implantation into TNBC tumors, the inherent properties of facilitate AZCE to penetrate the extracellular matrix and break through the basement membrane, enabling effective delivery of AZC to CSCs-enriched regions deep within the tumor. The released Zn induces mitochondrial dysfunction and amplifies reactive oxygen species (ROS) production. The redox cycling between Ce/Ce effectively depleted glutathione, which further increased ROS generation. Under near-infrared laser irradiation, Au nanorods initiated photothermal therapy, effectively ablating CSCs while amplifying catalytic reactions and ionic effects. This microneedle-mediated engineered bacteria delivery improved nanodrug penetration in tumor tissues, providing new insights for TNBC clinical treatment.

摘要

消除癌症干细胞(CSCs)对于三阴性乳腺癌(TNBC)的有效治疗至关重要。本研究合成了金@铈-锌复合核@壳纳米颗粒(Au@Zn/CeO),随后将其与()缀合以创建工程菌AZCE,然后将其与微针载体结合并冻干以获得AZCE-MN。将AZCE-MN植入TNBC肿瘤后,()的固有特性有助于AZCE穿透细胞外基质并突破基底膜,从而能够将AZC有效递送至肿瘤深处富含CSCs的区域。释放的锌诱导线粒体功能障碍并放大活性氧(ROS)的产生。Ce/Ce之间的氧化还原循环有效地消耗了谷胱甘肽,这进一步增加了ROS的产生。在近红外激光照射下,金纳米棒引发光热疗法,有效消融CSCs,同时放大催化反应和离子效应。这种微针介导的工程菌递送改善了纳米药物在肿瘤组织中的渗透,为TNBC临床治疗提供了新的见解。

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