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

Angew Chem Int Ed Engl. 2022 Jun 7;61(23):e202200535. doi: 10.1002/anie.202200535. Epub 2022 Apr 5.

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 (mPEG225 -b-PSSn , 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 mPEG225 -b-PSS26 . Such polyguanidine exhibited good in vitro performance in delivering different functional nucleic acids. The impressive therapeutic effects of mPEG225 -b-PSS26 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.

Keywords: Antibacterial; Antitumor; Controllable Disulfide Exchange Polymerization; Gene Delivery; Wound Healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disulfides
  • Mice
  • Neoplasms*
  • Nucleic Acids*
  • Polymerization
  • Sulfhydryl Compounds

Substances

  • Disulfides
  • Nucleic Acids
  • Sulfhydryl Compounds