HYPOTHESIS: Cationic polymers and their derivatives have garnered significant interest as advanced vectors for siRNA delivery. Recently, we developed a robust diblock copolymer featuring an innovative binding block and a stealth block that work synergistically to facilitate efficient delivery of biotherapeutics. However, the fundamental mechanisms underlying its superior delivery capacity remain to be fully elucidated. EXPERIMENTS: Since the binding block dominantly regulate the delivery performance, we synthesized a series of adapted copolymers, P(AAPBA FINDINGS: AAPBA and DMAPMA can bound to siRNA through reversible ester bonds and electrostatic interactions, respectively. The former enhanced siRNA release due to its responsive properties, while the cationic DMAPMA promoted endosomal escape of the complexes through its inherent interaction with membrane. Notably, only the rational combination of 20 units of each monomer, defined as copolymer P(AAPBA