RNAi delivery mediated by milk extracellular vesicles in colon cancer

• Published in: Molecular therapy. Nucleic acids Vol. 36; no. 3; p. 102644
• Main Authors: Santoro, Jessie, Nuzzo, Silvia, Soricelli, Andrea, Salvatore, Marco, Grimaldi, Anna Maria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.09.2025; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Aurora kinase A; colon cancer; diagnostic biomarker; gene silencing; milk extracellular vesicles; MT: Delivery Strategies; Original; siRNA; milk extracellular vesicles; colon cancer; gene silencing; siRNA; MT: Delivery Strategies; Aurora kinase A; diagnostic biomarker
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2025.102644

Small interfering RNA (siRNA) has emerged as a powerful tool for gene silencing, offering great potential for therapeutic applications. However, the clinical use of siRNA is limited by several challenges, including poor stability in biological fluids, off-target effects, and toxicity due to non-specific cellular uptake. To address these limitations, extracellular vesicles (EVs) derived from milk are being investigated as natural carriers to deliver siRNA and microRNA. These EVs offer advantages such as low immunogenicity, biocompatibility, and the ability to cross biological barriers. Here, we optimized methods for loading siRNA into milk-derived EVs (mEVS) and assessed their ability to protect siRNA from degradation while preserving its gene-silencing efficacy. We targeted a potential biomarker, Aurora kinase A (AURKA), known to be deregulated in many types of solid tumors, including colon cancer. Our results demonstrate that mEVs-loaded siRNA retains the stability and functionality of internalized siRNA, leading to efficient gene silencing in target cells. This approach highlights the potential of mEVs as a safe and valuable delivery system, overcoming key limitations of siRNA therapeutics and opening new avenues and opening new avenues for diagnostic and therapeutic strategies in colon cancer. [Display omitted] Grimaldi and colleagues show that bovine milk-derived extracellular vesicles can deliver siRNA targeting AURKA to colorectal cancer cells, achieving gene silencing without causing cytotoxicity or immune responses. This study emphasizes the potential of a biocompatible, scalable, and non-immunogenic platform for RNA-based cancer therapeutics using bovine milk-derived nanocarriers.