{"title":"Targeted siRNA Delivery Using Cetuximab-Conjugated Starch for Epidermal Growth Factor Receptor-Driven Head and Neck Squamous Cell Carcinoma.","authors":"Chen Benafsha, Limor Cohen, Leah Shimonov, Riki Goldbart, Tamar Traitel, Eliz Amar-Lewis, Ramesh Chintakunta, Manu Parasad, Uzi Hadad, Moshe Elkabets, Joseph Kost","doi":"10.1002/smsc.202500073","DOIUrl":null,"url":null,"abstract":"<p><p>Small interfering RNA (siRNA) therapy holds significant potential to disrupt oncogenic signaling pathways by targeting specific messenger RNA (mRNA) sequences. However, its clinical application is limited by challenges in developing effective delivery systems. In this study, starch, a biocompatible and biodegradable natural polysaccharide, is utilized as a carrier to enhance siRNA stability and delivery efficiency. By conjugating cetuximab to quaternized starch (Q-starch) complexed with the siRNA, an increased specificity is achieved toward cancer cells overexpressing the epidermal growth factor receptor (EGFR). This research encompasses the synthesis, characterization, and biological evaluation of these targeted complexes, which demonstrate efficient cellular uptake and on-target knockdown in vitro. Furthermore, these complexes exhibit notable tumor-specific accumulation, significantly enhancing the active targeting of EGFR-overexpressing tumors in vivo. These findings highlight the potential of the complexes to accumulate in EGFR-expressing head and neck squamous cell carcinoma, advancing the development of starch-based delivery systems and paving the way for further diagnostic and therapeutic applications.</p>","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 7","pages":"2500073"},"PeriodicalIF":8.3000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257885/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Small Science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/smsc.202500073","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Small interfering RNA (siRNA) therapy holds significant potential to disrupt oncogenic signaling pathways by targeting specific messenger RNA (mRNA) sequences. However, its clinical application is limited by challenges in developing effective delivery systems. In this study, starch, a biocompatible and biodegradable natural polysaccharide, is utilized as a carrier to enhance siRNA stability and delivery efficiency. By conjugating cetuximab to quaternized starch (Q-starch) complexed with the siRNA, an increased specificity is achieved toward cancer cells overexpressing the epidermal growth factor receptor (EGFR). This research encompasses the synthesis, characterization, and biological evaluation of these targeted complexes, which demonstrate efficient cellular uptake and on-target knockdown in vitro. Furthermore, these complexes exhibit notable tumor-specific accumulation, significantly enhancing the active targeting of EGFR-overexpressing tumors in vivo. These findings highlight the potential of the complexes to accumulate in EGFR-expressing head and neck squamous cell carcinoma, advancing the development of starch-based delivery systems and paving the way for further diagnostic and therapeutic applications.
期刊介绍:
Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.