Breakthroughs in the nanoparticle-mediated delivery of siRNA for breast cancer treatment.

Although breast cancer treatments have improved, challenges like tumor heterogeneity and drug resistance remain. RNA interference (RNAi), especially through small interfering RNA (siRNA), is a promising strategy to silence specific genes and improve clinical outcomes. However, the clinical translation of siRNA has been limited by barriers related to stability, biodistribution, cellular uptake, among others. Nanoparticle-based delivery systems have emerged as transformative platforms to address these limitations, enhancing siRNA protection, targeting, and intracellular release. This review discusses the major breakthroughs in nanoparticle-mediated siRNA delivery for breast cancer treatment, focusing on how innovations in nanocarrier design have enhanced siRNA stability, targeting, and therapeutic efficacy. We highlight key characteristics in RNA interference mechanisms, the evolution of computational tools for optimizing siRNA design, and the approval of RNAi-based therapies that laid the foundation for oncologic applications. Special emphasis is given to the development of lipid, polymeric, and inorganic nanoparticles engineered for efficient siRNA delivery, their role in overcoming drug resistance when combined with conventional therapies, and the current progress of clinical trials against solid tumors. By integrating nanotechnology and RNAi, these breakthroughs offer new opportunities for precise, durable, and personalized strategies in breast cancer treatment, with the potential to transform the current therapeutic landscape.