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By encapsulating the payload, prolonging systemic circulation, and incorporating surface functionalization (e.g., with targeting ligands), these systems dramatically enhance the tumor-specific accumulation and intracellular delivery efficiency of nucleic acid drugs [250, 251], This advanced delivery capability makes it feasible to precisely switch off resistance genes at the transcriptional or translational level, a principle convincingly demonstrated by studies in which functionalized nanoparticles successfully reversed tumor drug resistance through targeted gene silencing [252, 253]