Smart Nanoarchitectures for Precision RNA Delivery: Harnessing Endogenous and Exogenous Stimuli in Cancer Treatment.

RNA therapy holds great potential for cancer treatment owing to its ability to regulate gene expression precisely, thereby inhibiting tumor growth and metastasis. However, RNA delivery faces several physiological challenges, including rapid degradation by nucleases, limited cellular uptake, and inefficient intracellular release. To address these limitations, stimuli-responsive nanocarriers have been developed to enhance RNA delivery and improve therapeutic efficacy while minimizing side effects. These intelligent systems are designed to respond to specific endogenous or exogenous stimuli (, pH, redox potential, enzyme, light, magnetic fields, and ultrasound), enabling targeted delivery and controlled RNA release. This review highlights recent advances in the design and mechanisms of stimuli-responsive RNA nanocarriers, emphasizing key research findings and exploring future perspectives for their clinical translation.