TY - JOUR
T1 - Mechanochemical Drug Conjugation via pH-Responsive Imine Linkage for Polyether Prodrug Micelles
AU - Han, Sohee
AU - Lee, Joonhee
AU - Jung, Eunkyeong
AU - Park, Suebin
AU - Sagawa, Aoi
AU - Shibasaki, Yuji
AU - Lee, Dongwon
AU - Kim, Byeong Su
N1 - Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.
PY - 2021/3/15
Y1 - 2021/3/15
N2 - 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.
AB - 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.
KW - anionic ring-opening polymerization
KW - imine
KW - mechanochemistry
KW - polymer-drug conjugates
KW - post-polymerization modification
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U2 - 10.1021/acsabm.0c01437
DO - 10.1021/acsabm.0c01437
M3 - Article
C2 - 35014365
AN - SCOPUS:85101686550
SN - 2576-6422
VL - 4
SP - 2465
EP - 2474
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 3
ER -