Drug Delivery Systems for Breast Cancer Treatment: From Design Principles to Clinical Translation

Background/Objectives: Breast cancer is the most frequently diagnosed malignancy worldwide and remains a major cause of cancer-related mortality among women. Despite advances in screening, molecular classification, and systemic therapies, treatment of advanced and metastatic disease remains challenging because of tumor heterogeneity, multidrug resistance, systemic toxicity, limited drug selectivity, and inadequate penetration into the tumor microenvironment. This review aims to critically evaluate advanced drug delivery systems (DDSs) for breast cancer therapy, emphasizing the relationship between carrier design, tumor biology, therapeutic performance, and clinical translation. Methods: The recent literature on DDSs for breast cancer treatment was comprehensively reviewed, covering liposomes, polymeric nanoparticles and micelles, dendrimers, nanogels, lipid- and inorganic-based nanoparticles, extracellular vesicles, biomimetic platforms, and stimuli-responsive systems. Particular attention was given to active and passive targeting, controlled drug release, strategies for overcoming multidrug resistance and biological barriers, and combination approaches integrating chemotherapy with immunotherapy, gene therapy, and phototherapy. Clinically approved and clinical-stage nanomedicines were also considered. Results: Advanced DDSs can improve drug stability, pharmacokinetics, biodistribution, tumor accumulation, cellular uptake, and controlled release, potentially enhancing therapeutic efficacy while reducing systemic toxicity. Targeted, biomimetic, and stimuli-responsive platforms provide additional opportunities to address tumor heterogeneity, the tumor microenvironment, and therapeutic resistance. Several DDS-based nanomedicines have reached clinical use or advanced clinical development, demonstrating their translational potential. However, manufacturing scalability, reproducibility, long-term safety, regulatory requirements, and patient heterogeneity remain important barriers. Conclusions: Advanced DDSs represent promising tools for improving the precision and efficacy of breast cancer treatment. Future progress will require biologically informed carrier design, reproducible manufacturing, rigorous clinical validation, and patient stratification. Integrating nanomedicine with precision oncology may accelerate the clinical translation of next-generation DDSs and support more effective personalized therapeutic strategies.