Gold Nanoparticle Delivery of Glut1 SiRNA Facilitates Glucose Starvation Therapy in Lung Cancer

Abstract Glucose transporter protein‐1 (Glut1), is highly expressed in many cancer types and plays a crucial role in cancer progression through enhanced glucose transport. Its overexpression is associated with aggressive tumor behavior and poor prognosis. Herein, the nucleic acids modified gold nanoparticles (AuNPs) was synthesized to deliver small interfering RNA (siRNA) against Glut1 by microRNA 21 (miR‐21) triggers toehold‐mediated strand displacement reaction for lung cancer starvation therapy. Overexpression of miR‐21 triggers toehold‐mediated strand displacement, releasing the siRNA to knockdown of Glut1 in cancer cell instead of normal cell. Furthermore, the glucose oxidase‐like activity of the AuNPs accelerates intracellular glucose consumption, promoting cancer cell starvation. The engineered AuNPs@anti‐miR‐21/siGlut1 complex inhibits cancer cell proliferation, xenograft tumor growth and promotes apoptosis through glucose starvation and ROS cascade signaling, underscoring its potential as an effective therapeutic strategy for lung cancer.