Controllable Disulfide Exchange Polymerization of Polyguanidine for Effective Biomedical Applications by Thiol‐Mediated Uptake

Abstract New preparation methods of vectors are the key to developing the next generation of biomacromolecule delivery systems. In this study, a controllable disulfide exchange polymerization was established to obtain low‐toxicity and efficient bioreducible polyguanidines (mPEG 225 ‐ b ‐PSS n , n =13, 26, 39, 75, 105) by regulating the concentration of activated nucleophiles and reaction time under mild reaction conditions. The relationship between the degrees of polymerization and biocompatibility was studied to identify the optimal polyguanidine mPEG 225 ‐ b ‐PSS 26 . Such polyguanidine exhibited good in vitro performance in delivering different functional nucleic acids. The impressive therapeutic effects of mPEG 225 ‐ b ‐PSS 26 were further verified in the 4T1 tumor‐bearing mice as well as the mice with full‐thickness skin defects. Controllable disulfide exchange polymerization provides an attractive strategy for the construction of new biomacromolecule delivery systems.