RNAi delivery mediated by milk extracellular vesicles in colon cancer
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-spec...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125001982 |
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| author | Jessie Santoro Silvia Nuzzo Andrea Soricelli Marco Salvatore Anna Maria Grimaldi |
| author_facet | Jessie Santoro Silvia Nuzzo Andrea Soricelli Marco Salvatore Anna Maria Grimaldi |
| author_sort | Jessie Santoro |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0cc8a718d5eb4e0a9257cdc3088e4f68 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-0cc8a718d5eb4e0a9257cdc3088e4f682025-08-22T04:56:10ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-09-0136310264410.1016/j.omtn.2025.102644RNAi delivery mediated by milk extracellular vesicles in colon cancerJessie Santoro0Silvia Nuzzo1Andrea Soricelli2Marco Salvatore3Anna Maria Grimaldi4IRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Napoli, ItalyIRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Napoli, ItalyIRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Napoli, Italy; Department of Medical, Movement and Wellbeing Sciences, University of Naples Parthenope, Naples, ItalyIRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Napoli, ItalyIRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Napoli, Italy; Corresponding author: Anna Maria Grimaldi, IRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Napoli, Italy.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.http://www.sciencedirect.com/science/article/pii/S2162253125001982MT: Delivery Strategiesmilk extracellular vesiclescolon cancerAurora kinase AsiRNAgene silencing |
| spellingShingle | Jessie Santoro Silvia Nuzzo Andrea Soricelli Marco Salvatore Anna Maria Grimaldi RNAi delivery mediated by milk extracellular vesicles in colon cancer Molecular Therapy: Nucleic Acids MT: Delivery Strategies milk extracellular vesicles colon cancer Aurora kinase A siRNA gene silencing |
| title | RNAi delivery mediated by milk extracellular vesicles in colon cancer |
| title_full | RNAi delivery mediated by milk extracellular vesicles in colon cancer |
| title_fullStr | RNAi delivery mediated by milk extracellular vesicles in colon cancer |
| title_full_unstemmed | RNAi delivery mediated by milk extracellular vesicles in colon cancer |
| title_short | RNAi delivery mediated by milk extracellular vesicles in colon cancer |
| title_sort | rnai delivery mediated by milk extracellular vesicles in colon cancer |
| topic | MT: Delivery Strategies milk extracellular vesicles colon cancer Aurora kinase A siRNA gene silencing |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125001982 |
| work_keys_str_mv | AT jessiesantoro rnaideliverymediatedbymilkextracellularvesiclesincoloncancer AT silvianuzzo rnaideliverymediatedbymilkextracellularvesiclesincoloncancer AT andreasoricelli rnaideliverymediatedbymilkextracellularvesiclesincoloncancer AT marcosalvatore rnaideliverymediatedbymilkextracellularvesiclesincoloncancer AT annamariagrimaldi rnaideliverymediatedbymilkextracellularvesiclesincoloncancer |