Spatially Coordinated Delivery of siRNA and Peptide Antagonist by Using Quantum Dots for Synergetic Cancer Therapy

We present in this work a quantum-dot (QDs)-based delivery strategy for siRNA which shows pronounced improvements of stability against enzymatic degradation by ribonucleases, cellular uptake due to positively charge, and release from endosomes. The introduction of RNA-binding peptide to the QDs surface enables the dual delivery of the siRNA-peptide assembly. Briefly, EZH2-targeting peptide (EIP103) was first introduced to QDs surface via biotin-streptavidin interaction (PQDs), followed by incubation of siRNA that silences EZH2 (siEZH2). The self-assembly of EIP103 and siEZH2 on the QDs surface (RPQDs) was achieved via electrostatic attraction between the cationic EIP103 and the negatively charged siEZH2. The results revealed that the obtained RPQDs not only protect both EIP103 peptides and siEZH2 from enzymatic hydrolysis but also promote their endocytosis and endosome escape. This study demonstrates the feasibility of dual delivery and targeting of peptides and siRNA, offering a novel strategy for the synergistic cancer therapy.