Targeted siRNA Delivery Using Cetuximab‐Conjugated Starch for Epidermal Growth Factor Receptor‐Driven Head and Neck Squamous Cell Carcinoma

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.