Progress in nanotechnology-based strategies to enhance tamoxifen therapy for breast cancer management.

Breast cancer (BC) remains a major cause of cancer-related mortality among women worldwide, with estrogen receptor-positive (ER+) tumors representing the most common subtype. Tamoxifen (TMX), a selective estrogen receptor modulator, has been a cornerstone in ER+ BC therapy for decades. However, its clinical utility is hampered by its high lipophilicity, poor water solubility, systemic toxicity, off-target effects, and the emergence of resistance. In recent years, nanoparticle (NPs)-based drug delivery has emerged as a promising approach to surmount these challenges and enhance the therapeutic potential of TMX. These NPs not only improve solubility and bioavailability but also demonstrate validated outcomes such as resistance reversal, prolonged plasma half-life, significant tumor inhibition, and reduced systemic toxicity, thereby underscoring their clinical-translational potential in BC. This review critically analyzes the limitations of traditional TMX therapy and critically evaluates the role of various NPs-based strategies in overcoming these barriers. Furthermore, we explored the potential of multifunctional NPs to co-deliver TMX with other therapeutic agents to achieve synergistic effects and circumvent resistance. Overall, this review highlights the transformative potential of NPs-enabled TMX delivery systems and provides future perspectives on their clinical translation for better BC management.