DNA-Scaffolded Disulfide Redox Network for Programming Drug Delivery Kinetics.

Abstract

Dynamic covalent materials in response to specific stimuli enable generation of new structures by reversibly forming/breaking chemical bonds, holding a great potential for application in controlled drug release. However, it remains challenging to utilize dynamic covalent chemistry for programming drug delivery kinetics. Here, in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported by utilizing nucleic acids as scaffold of dynamic disulfide bonds. The constructed DdiSRN in response to redox-stimuli allows for selective release of loading cargos inside cancer cells. 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, programming drug delivery kinetics is realized with half-life t 1/2 decreasing from 8.3 h to 4.4 h, facilitating to keep the adequate drug concentration within its therapeutic window. Both in vitro and in vivo studies confirmed that co-delivery of DOX and siRNA in combination with fast drug release inside cells using this DdiSRN showed enhanced therapeutic effect on multidrug resistance cancer. This nontrivial therapeutic platform enabling kinetic control provides a good paradigm for precision cancer medicine.