Virus-Mimicking Nanoparticles for Precise Intracellular siRNA Delivery

Endosomal escape and precise subcellular accumulation remain key challenges in siRNA delivery. Conventional carriers achieve < 5% lysosomal escape and lack organelle specificity, limiting efficacy. Inspired by the dengue virus’s efficient intracellular transport, we designed virus-mimicking nanoparticles (pME@KNP) to replicate its dual-path strategy of pH-responsive lysosomal escape and ER targeting, ensuring high accumulation at the functional site. Thus, this virus-mimicking strategy optimizes siRNA therapeutics by overcoming delivery barriers and ensuring precise subcellular targeting.