Microbiome-targeted nanoplatforms and engineering approaches in breast cancer therapy.

Breast cancer (BC) presents persistent therapeutic challenges due to tumor heterogeneity, therapy resistance, and immune dysfunction, further compounded by emerging evidence of microbiome involvement in disease progression. Pathogenic bacteria such as Fusobacterium nucleatum have been implicated in modulating immune evasion, remodeling the extracellular matrix, and influencing therapy outcomes. Conventional microbiome-modulating strategies (e.g., antibiotics, probiotics) suffer from non-specificity and potential dysbiosis. Nanomaterial (NM)-based microbiome modulation offers a transformative alternative by enabling: targeted elimination of tumor-associated pathogens (e.g., Gal/GalNAc-functionalized nanoparticles for F. nucleatum), bacterial membrane-coated nanoplatforms for precision antimicrobial delivery, and multifunctional nanosystems that modulate the tumor microenvironment (TME) while preserving beneficial microbiota. This review explores NM-based microbiome modulation across BC contexts, including localized drug delivery, immunomodulation, and microbial niche editing. Highlighted strategies include lipid-based antimicrobial nanoparticles (NP), metallic NPs enhancing therapy sensitivity, and Traditional Chinese Medicine (TCM)-inspired nanoformulations for microbiome balance. Synergies with chemotherapy, immunotherapy, and radiotherapy are evaluated, alongside preclinical findings demonstrating improved tumor control and microbiome resilience. Finally, challenges in clinical translation, including toxicity, immunogenicity, and scalability, are discussed, with future directions emphasizing smart nanosystems capable of microbiome-responsive, biomarker-guided, and immune-integrated interventions in BC therapy.