Polysaccharide-functionalized metallic nanoparticles (MFNPs), including gold (Au), silver (Ag), and iron oxide (Fe 3 O 4 ), have emerged as promising nanocarriers for small interfering RNA (siRNA) delivery in cancer nanomedicine. Functionalization with polysaccharides enhances their biocompatibility, targeting capability, and therapeutic efficacy. This review provides a comprehensive overview of the design, mechanisms, and applications of polysaccharide-functionalized Au, Ag, and Fe 3 O 4 nanoparticles as siRNA delivery vehicles, emphasizing the integration of Artificial intelligence (AI) for their optimization in cancer therapy. We systematically explore the types of metallic nanoparticles used, their functionalization strategies with various polysaccharides, and the mechanistic pathways involved in siRNA delivery. We further highlight the role of AI and machine learning (ML) in predicting nanoparticle stability, improving siRNA loading and release, enhancing targeting precision, and enabling personalized nanomedicine approaches. Polysaccharide-coated MFNPs demonstrate improved siRNA protection, cellular uptake, endosomal escape, and gene silencing efficiency. AI-driven facilitate the rational design of nanocarriers by predicting physicochemical properties, biological interactions, and patient-specific responses. Preclinical and emerging clinical evidence support their potential as next-generation cancer therapeutics. Polysaccharide-functionalized Au, Ag, and Fe 3 O 4 nanoparticles, empowered by AI-based optimization, represent a cutting-edge strategy for siRNA delivery in cancer nanomedicine. Future research should focus on translating these nanocarriers into clinical applications through multidisciplinary collaboration and advanced computational tools.
Esmaeilpour et al. (2026) studied this question.