Potential Applications of ROS-Responsive Silk Fibroin Materials in Smart Drug Delivery Systems

Silk fibroin (SF) is a promising drug carrier because of its unique macromolecular structure and excellent biocompatibility and biodegradability. In this study, we developed a responsive SF material by introducing reactive oxygen species (ROS)-cleavable thioketal (TK) between the SF macromolecular chains. TK was synthesized with carboxyl (−COOH) groups at both ends of the molecules, and its C–S bonds could be cleaved in an ROS-rich environment. The molecular weight and chemical structure of TK were identified using mass spectrometry and 1H-nuclear magnetic resonance. Subsequently, we prepared SF/TK films and found that KO2 treatment resulted in a significant change in their morphology and mechanical properties relative to unmodified SF films when the SF/TK mass ratios ranged from 100:3 to 100:5. Based on these findings, a camptothecin (CPT)-loaded SF/TK drug carrier was developed at an SF/TK mass ratio of 100:3 by self-assembly. Release kinetics demonstrated that the release rate of CPT from SF/TK nanoparticles was 2.5 times higher than that from SF microspheres in the KO2 environment. There were distinct changes in the surface morphologies of the nanoparticles. This study suggests that introducing TK can confer ROS-responsive cleavage on SF materials, which have potential applications for smart drug delivery systems.