Process and Mechanism of Nanocarrier-Loaded dsRNA Penetrating the Insect Cuticle: Theoretical Foundation for...

RNA interference (RNAi) provides a powerful tool for functional gene identification and pest management, and nanocarriers have recently enabled noninvasive transdermal RNAi delivery. However, the mechanism of nanocarrier-mediated double-stranded RNA (dsRNA) translocation across the insect cuticle remains unknown. We used a star cationic polymer (SPc) as a model to visualize this process and elucidate its interactions with aphid cuticle components. SPc self-assembled with dsRNA to form stable nanocomplexes via electrostatic and hydrophobic interactions. This assembly altered the wax layer morphology and increased chitin interfibrillar spacing, creating a permissive interface for dsRNA translocation. SPc also increased the contact area, reduced the contact angle, and significantly improved penetration through artificial wax/cuticle. Furthermore, SPc interacted with major cuticle components through various intermolecular forces, causing wax dissolution and reduced interfacial resistance at the chitin layer. These findings demonstrate that nanocarrier-mediated wax dissolution and chitin-layer barrier reduction facilitate dsRNA translocation across the insect cuticle, providing a theoretical foundation for transdermal delivery systems.