Implantable Microneedles Loaded with Nanoparticles Surface Engineered <i>Escherichia coli</i> for Efficient Eradication of Triple-Negative Breast Cancer Stem Cells
Weinan Zhang, Yechun Jiang, Litao Liu, Hui Shen, Xianyu Huang, Wang Zheng, Zhaoyou Chu, Wanni Wang, Yanchuan Guo, Haisheng Qian
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 Escherichia coli ( E. coli ) 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 E. coli 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 2+ induces mitochondrial dysfunction and amplifies reactive oxygen species (ROS) production. The redox cycling between Ce 3+ /Ce 4+ 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.