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DNA‐Scaffolded Disulfide Redox Network for Programming Drug‐Delivery Kinetics
Author(s) -
Ji Wei,
Li Xiaodan,
Xiao Mingshu,
Sun Yueyang,
Lai Wei,
Zhang Hongbo,
Pei Hao,
Li Li
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100149
Subject(s) - kinetics , chemistry , covalent bond , drug delivery , dna , combinatorial chemistry , redox , disulfide bond , biophysics , nucleic acid , polymerization , controlled release , nanotechnology , materials science , biochemistry , polymer , organic chemistry , physics , quantum mechanics , biology
In response to specific stimuli, dynamic covalent materials enable the generation of new structures by reversibly forming/breaking chemical bonds, thus showing great potential for application in controlled drug release. However, using dynamic covalent chemistry to program drug‐delivery kinetics remains challenging. Herein, an in situ polymerization‐generated DNA‐scaffolded disulfide redox network (DdiSRN) is reported in which nucleic acids are used as a scaffold for dynamic disulfide bonds. The constructed DdiSRN allows selective release of loading cargos inside cancer cells in response to redox stimuli. Moreover, the density of disulfide bonds in network can be tuned by precise control over their position and number on DNA scaffolds. As a result, drug‐delivery kinetics can be programmed with a half‐life, t 1/2 , decreasing from 8.3 to 4.4 h, thus facilitating keeping an adequate drug concentration within the therapeutic window. Both in vitro and in vivo studies confirm that co‐delivery of DOX and siRNA in combination with fast drug release inside cells using this DdiSRN enhances the therapeutic effect on multidrug‐resistant cancer. This nontrivial therapeutic platform enabling kinetic control provides a good paradigm for precision cancer medicine.