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Fabrication of Reduction‐Responsive Star‐Shaped Amphiphilic Block Copolymers with Click Coupling‐Generated Block Junctions toward Enhanced Therapeutic Efficacy
Author(s) -
Wang Mingqi,
Wang Yunfei,
Zhao Sijie,
Zhang Xiaolong,
Wei Hua
Publication year - 2018
Publication title -
macromolecular chemistry and physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.57
H-Index - 112
eISSN - 1521-3935
pISSN - 1022-1352
DOI - 10.1002/macp.201800061
Subject(s) - nanocarriers , amphiphile , copolymer , combinatorial chemistry , click chemistry , chemistry , drug delivery , disulfide bond , materials science , nanotechnology , organic chemistry , polymer , biochemistry
Abstract Incorporation of the reducible disulfide links into delivery systems has been repeatedly highlighted to realize, elegantly, the tradeoff between extracellular stability and intracellular high therapeutic efficacy. Of all the reported introducing strategies, esterification, seemingly the most extensively‐adopted one, suffers from relatively low yield, especially for the esterification coupling between two macromolecules, due to the low condensation efficiency. To improve the coupling efficiency, Cu(I)‐catalyzed azide−alkyne cycloaddition (CuAAc) click coupling with high efficiency and high selectivity is used to incorporate disulfide links to the star‐shaped amphiphilic block copolymers in this study. Interestingly, besides such synthetic advantages, the click coupling‐introduced disulfide joints further endow the resulting star‐shaped copolymer‐based nanocarriers with higher therapeutic efficacy than the analogues containing esterification‐generated disulfide links, in terms of better buffering capacity, greater selective drug release in reducing over nonreducing environments, and higher in vitro cytotoxicity. The disclosed effect of introducing strategy of disulfide link on the delivery efficacy of the drug carriers provides new insights into the structure–property relationship of reduction‐sensitive delivery systems, as well as offering new opportunities for the future design and development of intelligent nanocarriers toward enhanced therapeutic efficacy.