Nanoparticle-Based miRNA Therapeutics in Breast Cancer Highlighting Design Strategies and Translational Potential
: Breast cancer remains one of the leading causes of cancer-related mortality worldwide, with its marked molecular heterogeneity and therapeutic resistance continuing to limit long-term clinical success. Although advances in targeted therapies have improved patient outcomes, tumor recurrence, systemic toxicity, and drug resistance remain major clinical challenges. MicroRNAs (miRNAs) have emerged as promising therapeutic molecules because they regulate multiple oncogenic pathways involved in proliferation, apoptosis, epithelial–mesenchymal transition, metastasis, and therapy resistance. Preclinical studies have demonstrated that restoring tumor-suppressive miRNAs or inhibiting oncogenic miRNAs can suppress tumor growth, reduce metastatic potential, and enhance treatment sensitivity. However, their clinical application is hindered by poor stability, rapid enzymatic degradation, limited cellular uptake, and inefficient intracellular delivery. Recent advances in nanomedicine have enabled the development of multifunctional nanoparticle platforms that effectively address these limitations. Lipid nanoparticles, polymeric nanoparticles, dendrimers, and inorganic nanocarriers have demonstrated the ability to protect miRNAs from degradation, prolong systemic circulation, enhance tumor-specific accumulation, facilitate cellular uptake, and promote endosomal escape for efficient cytoplasmic release. Moreover, targeted and stimuli-responsive nanocarriers, as well as combination strategies integrating miRNAs with conventional therapeutics, have shown encouraging therapeutic efficacy in preclinical breast cancer models. This review summarizes recent advances in nanoparticle-mediated miRNA delivery systems for breast cancer, highlighting the biological roles of therapeutic miRNAs, the design and performance of current nanocarriers, and their translational potential. Current challenges and future perspectives for the clinical implementation of miRNA-based nanomedicine are also discussed. Overall, nanoparticle-enabled miRNA therapeutics represent a promising platform for advancing precision medicine and next-generation personalized treatment strategies for breast cancer.