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RNA interference (RNAi) has emerged as a transformative approach for cancer therapy, enabling precise gene silencing through small interfering RNA (siRNA). However, the clinical application of siRNA-based treatments faces challenges such as rapid degradation, inefficient cellular uptake, and immune system clearance. Nanotechnology-enhanced siRNA delivery has revolutionized cancer therapy by addressing these limitations, improving siRNA stability, tumor-specific targeting, and therapeutic efficacy. Recent advancements in nanocarrier engineering have introduced innovative strategies to enhance the safety and precision of siRNA-based therapies, offering new opportunities for personalized medicine. This review highlights three key innovations in nanotechnology-enhanced siRNA delivery: artificial intelligence (AI)-driven nanocarrier design, multifunctional nanoparticles for combined therapeutic strategies, and biomimetic nanocarriers for enhanced biocompatibility. AI-driven nanocarriers utilize machine learning algorithms to optimize nanoparticle properties, improving drug release profiles and minimizing off-target effects. Multifunctional nanoparticles integrate siRNA with chemotherapy, immunotherapy, or photothermal therapy, enabling synergistic treatment approaches that enhance therapeutic outcomes and reduce drug resistance. Biomimetic nanocarriers, including exosome-mimicking systems and cell-membrane-coated nanoparticles, improve circulation time, immune evasion, and targeted tumor delivery. These innovations collectively enhance the precision, efficiency, and safety of siRNA-based cancer therapies. The scope and novelty of these advancements lie in their ability to overcome the primary barriers of siRNA delivery while paving the way for clinically viable solutions. This review provides a comprehensive analysis of the latest developments in nanocarrier fabrication, preclinical and clinical studies, and safety assessments. By integrating AI-driven design, multifunctionality, and biomimicry, nanotechnology-enhanced siRNA delivery holds immense potential for the future of precision cancer therapy.
Esmaeilpour et al. (Mon,) studied this question.