pH-labile sheddable block copolymers by RAFT polymerization: Synthesis and potential use as siRNA conjugates

Well-defined amphiphilic block copolymers composed of hydrophilic and hydrophobic blocks linked through an acid-labile acetal bond were synthesized directly by RAFT polymerization. Potential use of the pH-labile shedding behavior of the copolymers was demonstrated by conjugating a thiol-modified siRNA to ω-pyridyldisulfide modified poly(ethylene glycol)-b-poly(cholesteryl methacrylate) (PEG-b-PCMA). The resultant triblock polymer, PEG-b-PCMA-b-siRNA proved to release PCMA-b-siRNA and siRNA in acidic and reductive conditions, respectively.