Mechanochemical Drug Conjugation via pH-Responsive Imine Linkage for Polyether Prodrug Micelles

Sohee Han, Joonhee Lee, Eunkyeong Jung, Suebin Park, Aoi Sagawa, Yuji Shibasaki, Dongwon Lee, Byeong Su Kim

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Prodrug-type polymer-drug conjugates based on highly biocompatible functional polyethers are developed through mechanochemical post-polymerization modification. Herein, we design functional epoxide monomers of ethoxyethyl glycidyl ether (EEGE) and azidohexyl glycidyl ether (AHGE) and synthesize diblock copolyethers of PEEGE-b-PAHGE via sequential anionic ring-opening polymerization. Subsequent conversion of the functional monomers to the corresponding hydroxyl and amine groups allows for the preparation of double hydrophilic block copolyethers. Most notably, mechanochemical modification allows for the conjugation of these polymers with a highly hydrophobic and potent anticancer agent, cinnamaldehyde, through an imine linkage. The self-assembly of the resulting polymer-drug conjugates into polymeric micelles is characterized by dynamic light scattering and atomic force microscopy. The pH-responsive cleavage of the imine linkages under acidic conditions leads to the release of cinnamaldehyde with a concomitant disassembly of the polymeric micelles. The superior biocompatibility coupled with the solvent-less mechanochemical conjugation approach provides a convenient means to introduce various therapeutics for smart drug delivery.

Original languageEnglish
Pages (from-to)2465-2474
Number of pages10
JournalACS Applied Bio Materials
Issue number3
Publication statusPublished - 2021 Mar 15

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biomaterials
  • Biomedical Engineering
  • Biochemistry, medical


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