关键词：聚阳离子结构；siRNA
摘 要：This chapter reviews our strategy for optimization of polycationic structures to improve siRNA delivery and reduce carrier toxicitiy. Improvement in carrier design is realized by modulating the number of repeating aminoethylene (RA) units in the side chain of a poly(aspartamide) derivative (PAsp(R)). Results reveal that the number of RA units in the PAsp(R) side chains affects their protonation behavior between extracellular and endosomal pHs in a distinctive "odd-even" manner. PAsp(R)s with even-numbered RA units induce acidic pH-responsive membrane disruption based on substantially increased protonation at the endosomal pH of 5.5. Ultimately, PAsp(R) with 4 RA units in each side chain demonstrated excellent transfection of siRNA due to accelerated endosomal escape as well as stable siRNA complexation.