Anti-prostate-specific membrane antigen (PSMA) aptamer-mediated small interfering (si)RNA delivery. (a) Schematic of anti-PSMA aptamer-streptavidin-siRNA conjugates. The 27-mer Dicer substrate RNA duplex and RNA aptamers were chemically conjugated with a biotin group. Thus, two biotinylated siRNAs and two aptamers were non-covalently assembled via a streptavidin platform. (b) Schematic of the first generation anti-PSMA aptamer-siRNA chimeras. The 2'-Fluoro-modified aptamer and siRNA sense strand were co-transcribed, followed by annealing of the complementary siRNA antisense strand to complete the chimeric molecule. (c) Schematic of the optimized second generation chimeras. Compared with the first generation chimeras, the aptamer portion of the chimera was truncated from 71 to 39 nucleotides, and the sense and antisense strands of the siRNA portion were swapped. A 2 nucleotide (UU)-overhang and a polyethylene glycol tail were added to the 3'-end of the guide strand and the 5'-end of passenger strand, respectively.