Polymer-Metal Nanoparticle Hybrid Systems for Targeted Breast Cancer Therapy: Advances and Clinical Translation.

Breast cancer remains a challenging malignancy in modern oncology among women worldwide and a leading cause of cancer-related mortality. Despite advances in chemotherapy, endocrine therapy, targeted therapeutics, and immunotherapy, treatment outcomes remain limited by systemic toxicity, poor tumor selectivity, multidrug resistance, and disease recurrence. Nanotechnology-based drug delivery systems have emerged as promising approaches to overcome these limitations. Among them, polymer-metal hybrid nanoparticles combine the biocompatibility and controlled drug-release properties of polymeric carriers with the unique optical, photothermal, magnetic, catalytic, and imaging capabilities of metallic nanoparticles. This narrative review highlights the synergistic advantages of polymer-metal hybrid nanoparticles and their emerging role in targeted breast cancer therapy. Recent advances in their design, synthesis, surface functionalization, targeting strategies, and multifunctional applications have expanded their potential for targeted drug delivery, photothermal therapy, and theranostic interventions. These hybrid nanoplatforms facilitate passive and active tumor targeting, support stimuli-responsive drug release, and enable integrated diagnostic and therapeutic functions. Particular emphasis is placed on their ability to modulate the tumor microenvironment and overcome multidrug resistance in clinically relevant breast cancer subtypes, including human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-positive, and triple-negative breast cancers. Preclinical studies demonstrate enhanced tumor accumulation, improved antitumor efficacy, reduced off-target toxicity, and superior imaging performance compared with conventional therapies. Despite these advances, challenges remain in large-scale manufacturing, reproducibility, long-term safety evaluation, pharmacokinetic variability, and regulatory approval. Overall, polymer-metal hybrid nanoparticles represent a versatile and promising nanomedicine platform for precision breast cancer management, with continued advances in nanoparticle engineering, safety assessment, and clinical validation expected to facilitate their successful translation into personalized oncology.