Fig. 1: Preparation of gold nanoparticle/multi-functional 3D DNA self-assembled multilayer core/shell nanostructure (siRNA/Ap-CS) and its application for targeted siRNA delivery and controlled release within tumor cells.

Step I, functionalization of AuNP with thiol-modified anchoring DNA complementary to miRNA (ADC), forming ADC-AuNP; Step II, binding of elongated siRNA to AuNP-confined ADC, producing siRNA/ADC-AuNP; Step III, programmed positioning of aptamer (Ap)-integrated Y-shaped backbone-rigidified triangular DNA bricks (Ap-YTDB) onto siRNA/ADC-AuNP, leading to the formation of expected biocompatible core/shell nanostructure, siRNA/Ap-CS; Step IV, aptamer-mediated specific cell recognition and endocytosis; Step V, intracellular controlled release of encapsulated siRNAs by the strand displacement initiated by endogenous miRNAs.