Implantable Microneedles Loaded with Nanoparticles Surface Engineered <i>Escherichia coli</i> for Efficient Eradication of Triple-Negative Breast Cancer Stem Cells.

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 <i>Escherichia coli</i> (<i>E. coli</i>) 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 <i>E. coli</i> 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 Zn²⁺ induces mitochondrial dysfunction and amplifies reactive oxygen species (ROS) production. The redox cycling between Ce³⁺/Ce⁴⁺ 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.